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1.
Rev Paul Pediatr ; 39: e2019290, 2021.
Article in Portuguese, English | MEDLINE | ID: mdl-32638943

ABSTRACT

OBJECTIVE: To describe the case of a child who presented hemophagocytic lymphohistiocytosis (HLH) associated with acute monocytic leukemia after chemotherapy, with hemophagocytosis caused by leukemic cells. CASE DESCRIPTION: In a university hospital in Southern Brazil, a 3-year-old female was diagnosed with acute monocytic leukemia with normal karyotype. The chemotherapy regimen was initiated, and she achieved complete remission six months later, relapsing after four months with a complex karyotype involving chromosomes 8p and 16q. The bone marrow showed vacuolated blasts with a monocytic aspect and evidence of hemophagocytosis. The child presented progressive clinical deterioration and died two months after the relapse. COMMENTS: HLH is a rare and aggressive inflammatory condition characterized by cytopenias, hepatosplenomegaly, fever, and hemophagocytosis in the bone marrow, lymph nodes, spleen, and liver. Although rare, malignancy-associated HLH (M-HLH) is fatal. The patient in this case report met five out of the eight established criteria for HLH. The evolution of the patient's karyotype, regardless of the diagnostic profile, seemed secondary to the treatment for acute monocytic leukemia. In this case, the cytogenetic instability might have influenced the abnormal behavior of leukemic cells. This is a rare case of HLH in a child with acute monocytic leukemia.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Leukemia, Monocytic, Acute/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Brazil , Child, Preschool , Fatal Outcome , Female , Humans , Leukemia, Monocytic, Acute/diagnosis , Leukemia, Monocytic, Acute/genetics , Leukemia, Monocytic, Acute/pathology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/pathology
2.
Article in English, Portuguese | LILACS, Sec. Est. Saúde SP | ID: biblio-1136755

ABSTRACT

ABSTRACT Objective: To describe the case of a child who presented hemophagocytic lymphohistiocytosis (HLH) associated with acute monocytic leukemia after chemotherapy, with hemophagocytosis caused by leukemic cells. Case description: In a university hospital in Southern Brazil, a 3-year-old female was diagnosed with acute monocytic leukemia with normal karyotype. The chemotherapy regimen was initiated, and she achieved complete remission six months later, relapsing after four months with a complex karyotype involving chromosomes 8p and 16q. The bone marrow showed vacuolated blasts with a monocytic aspect and evidence of hemophagocytosis. The child presented progressive clinical deterioration and died two months after the relapse. Comments: HLH is a rare and aggressive inflammatory condition characterized by cytopenias, hepatosplenomegaly, fever, and hemophagocytosis in the bone marrow, lymph nodes, spleen, and liver. Although rare, malignancy-associated HLH (M-HLH) is fatal. The patient in this case report met five out of the eight established criteria for HLH. The evolution of the patient's karyotype, regardless of the diagnostic profile, seemed secondary to the treatment for acute monocytic leukemia. In this case, the cytogenetic instability might have influenced the abnormal behavior of leukemic cells. This is a rare case of HLH in a child with acute monocytic leukemia.


RESUMO Objetivo: Descrever um caso de um paciente pediátrico que apresentou linfo-histiocitose hemofagocítica (LHH) associada à leucemia monocítica aguda pós-quimioterapia, com hemofagocitose causada pelas próprias células leucêmicas. Descrição do caso: Em um hospital universitário do Sul do Brasil, uma menina de três anos foi diagnosticada com leucemia monocítica aguda com cariótipo normal. Após receber protocolo quimioterápico, atingiu remissão seis meses depois do início do tratamento, recaíndo quatro meses após com um cariótipo complexo envolvendo ambos os cromossomos, 8p e 16q. A medula óssea mostrava-se infiltrada por células blásticas vacuolizadas com aspecto monocítico, com evidências de hemofagocitose. A criança apresentou um declínio clínico progressivo e dois meses após a recaída foi a óbito. Comentários: A LHH é uma condição inflamatória rara e agressiva caracterizada por citopenias, hepatoesplenomegalia, febre e hemofagocitose na medula óssea, linfonodos, baço e fígado. A LHH associada a doenças malignas, embora seja uma condição rara, é potencialmente fatal. A paciente deste caso apresentou cinco dos oito critérios estabelecidos para o diagnóstico de LHH. A evolução do cariótipo do paciente, independentemente do perfil do diagnóstico, pareceu ser secundária ao tratamento da leucemia monocítica aguda, sendo que a instabilidade citogenética pode ter influenciado o comportamento atípico observado nas células leucêmicas. Este é um dos raros casos de LHH em uma criança com leucemia monocítica aguda.


Subject(s)
Humans , Female , Child, Preschool , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Leukemia, Monocytic, Acute/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Brazil , Leukemia, Monocytic, Acute/diagnosis , Leukemia, Monocytic, Acute/genetics , Leukemia, Monocytic, Acute/pathology , Fatal Outcome , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/pathology
3.
Genet Mol Res ; 14(2): 5630-41, 2015 May 25.
Article in English | MEDLINE | ID: mdl-26125761

ABSTRACT

Leukemia stem cells (LSCs) are regarded as the origin of leukemia and its recurrence. Side population (SP) cells possess some intrinsic stem cell properties and contain numerous LSCs. In this study, we examined the prognostic significance of cluster differentiation 47 (CD47) and identified the appropriate target for eliminating LSCs. We determined the percentage of SP cells in a THP-1 cell population and analyzed CD47 expression in different cell subsets. We then explored whether CD47 affected the phagocytic ability of macrophages to LSCs in vitro. Finally, the effect of anti-CD47 monoclonal antibodies, alone or combination with cytarabine, against leukemic cells was evaluated in vitro and in vivo to identify the optimal targets for the treatment of leukemia. We observed an SP sub-fraction at low frequency (1.81 ± 0.99%), which was a likely candidate for LSC enrichment. CD47 was more highly expressed on THP-1 LSCs (P < 0.05) and was an independent predictor of survival and refractory disease in THP-1-engrafted mice. Furthermore, the anti-CD47 monoclonal antibody stimulated preferential phagocytosis of LSCs by macrophages in vitro. Finally, single or combination treatment of THP-1 LSC-engrafted mice with cytarabine and anti-CD47 antibody resulted in targeting of LSCs and depletion of leukemia cells. These findings suggest that CD47 is an antibody target in LSCs and combination treatment with cytarabine and anti-CD47 monoclonal antibody represents an attractive option for the therapeutic targeting of acute monocytic leukemia.


Subject(s)
Antibodies, Monoclonal/administration & dosage , CD47 Antigen/immunology , Leukemia, Monocytic, Acute/drug therapy , Animals , Antibodies, Monoclonal/immunology , Cell Differentiation/drug effects , Cell Line, Tumor , Combined Modality Therapy , Cytarabine/administration & dosage , Humans , Leukemia, Monocytic, Acute/immunology , Leukemia, Monocytic, Acute/pathology , Macrophages/drug effects , Mice , Neoplastic Stem Cells/drug effects , Phagocytosis , Prognosis , Xenograft Model Antitumor Assays
4.
Biomedica ; 34(4): 589-97, 2014.
Article in English | MEDLINE | ID: mdl-25504248

ABSTRACT

INTRODUCTION: Photodynamic therapy (PDT) using 5-aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) constitutes an interesting alternative for cutaneous leishmaniasis treatment. OBJECTIVE: To evaluate the production of PpIXbased on the administration of ALA and MAL and the effect of ALA-PDTat cellular level on non-infected and infected THP-1 cells using Leishmania ( Viannia ) panamensis or Leishmania ( Leishmania ) infantum (syn Leishmania chagasi ) parasites. MATERIALS AND METHODS: Protoporphyrin IX (PpIX) production and mitochondrial colocalization were evaluated by confocal microscopy. Cell toxicities were evaluated after treatment with the compounds, followed by light irradiation (597-752 nm) at 2.5 J/cm 2 fluency using a colorimetric MTT assay for THP-1 cells and a standard microscopic analysis of parasites. RESULTS were expressed as compound concentration activity against 50% of cells or parasites (CC 50 or IC 50 ). RESULTS: ALA or MAL induced an endogenous PpIX with a red fluorescence localized mainly in the mitochondria inside human cells. ALA and MAL-PDT induced a similar range of toxicities on THP-1 cells (CC 50 0.16 ± 0.01 mM and 0.33 ± 0.019 mM, respectively) without any apparent inhibition of intracellular parasites in the infected cells as compared to untreated controls. Exogenous PpIX-PDT was toxic to THP-1 cells (CC 50 0.00032 ± 0.00002 mM), L. (L.) infantum (IC 50 0.003 ± 0.0001 mM) and L. (V.) panamensis (IC 50 0.024 ± 0.0001 mM) promastigotes. CONCLUSIONS: Despite the effectiveness of exogenous PpIX on promastigotes and the production of PpIX by human infected cells, treatment with ALA or MAL before irradiation was unable to completely destroy L. (L.) infantum or L. (V.) panamensis intracellular amastigotes.


Subject(s)
Aminolevulinic Acid/analogs & derivatives , Aminolevulinic Acid/pharmacology , Leishmania guyanensis/drug effects , Leishmania infantum/drug effects , Monocytes/drug effects , Photochemotherapy , Photosensitizing Agents/pharmacology , Protoporphyrins/analysis , Subcellular Fractions/drug effects , Aminolevulinic Acid/radiation effects , Amphotericin B/pharmacology , Cell Line, Tumor , Colorimetry , Humans , Leukemia, Monocytic, Acute/pathology , Lysosomes/chemistry , Microscopy, Fluorescence , Mitochondria/chemistry , Monocytes/parasitology , Monocytes/ultrastructure , Photosensitizing Agents/radiation effects , Species Specificity , Subcellular Fractions/chemistry
5.
Biomédica (Bogotá) ; Biomédica (Bogotá);34(4): 589-597, oct.-dic. 2014. ilus, graf
Article in English | LILACS | ID: lil-730943

ABSTRACT

Introduction: Photodynamic therapy (PDT) using 5-aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX) constitutes an interesting alternative for cutaneous leishmaniasis treatment. Objective: To evaluate the production of PpIXbased on the administration of ALA and MAL and the effect of ALA-PDTat cellular level on non-infected and infected THP-1 cells using Leishmania ( Viannia ) panamensis or Leishmania ( Leishmania ) infantum (syn Leishmania chagasi ) parasites. Materials and methods: Protoporphyrin IX (PpIX) production and mitochondrial colocalization were evaluated by confocal microscopy. Cell toxicities were evaluated after treatment with the compounds, followed by light irradiation (597-752 nm) at 2.5 J/cm 2 fluency using a colorimetric MTT assay for THP-1 cells and a standard microscopic analysis of parasites. Results were expressed as compound concentration activity against 50% of cells or parasites (CC 50 or IC 50 ). Results: ALA or MAL induced an endogenous PpIX with a red fluorescence localized mainly in the mitochondria inside human cells. ALA and MAL-PDT induced a similar range of toxicities on THP-1 cells (CC 50 0.16±0.01mM and 0.33±0.019 mM, respectively) without any apparent inhibition of intracellular parasites in the infected cells as compared to untreated controls. Exogenous PpIX-PDT was toxic to THP-1 cells (CC 50 0.00032±0.00002 mM), L. (L.) infantum (IC 50 0.003±0.0001 mM) and L. (V.) panamensis (IC 50 0.024±0.0001 mM) promastigotes. Conclusions: Despite the effectiveness of exogenous PpIX on promastigotes and the production of PpIX by human infected cells, treatment with ALA or MAL before irradiation was unable to completely destroy L. (L.) infantum or L. (V.) panamensis intracellular amastigotes.


Introducción. El tratamiento fotodinámico con ácido 5-aminolevulínico como inductor de la protoporfirina IX (ALA-PpIX) constituye una alternativa interesante en el tratamiento de la leishmaniasis cutánea. Objetivo. Evaluar la producción de protoporfirina IX (PpIX) a partir de la administración de ALA o MAL y el efecto de la PDT con ALA a nivel celular en células THP-1 no infectadas e infectadas con Leishmania ( Viannia ) panamensis o Leishmania ( Leishmania ) infantum (syn. Leishmania chagasi ). Materiales y métodos. La producción de protoporfirina IX y su ‘colocalización´ mitocondrial se evaluaron mediante microscopía ‘confocal´. Se evaluó la toxicidad celular después del tratamiento con los compuestos y la aplicación de irradiación de luz (597-752 nm) en una fluencia de 2,5 J/cm 2 mediante el empleo de la prueba colorimétrica con metil-tiazol-tetrazolio (MTT) en las células, y de métodos microscópicos estándar en los parásitos. Los resultados se expresaron como la concentración del compuesto activo en el 50 % de las células o parásitos (CC 50 o CI 50 ). Resultados. El ácido aminolevulínico o el metil-5-aminolevulinato indujeron la protoporfirina IX endógena en células humanas, y se observó fluorescencia de color rojo en las mitocondrias. La actividad del ácido aminolevulínico y del metil-5-aminolevulinato utilizados con terapia fotodinámica fue similar en las células THP-1 (CC 50 0,16±0,01 mM y 0,33±0,019 mM, respectivamente) y, aparentemente, no inhibió los parásitos en las células infectadas, en comparación con los controles. El tratamiento exógeno con protoporfirina IX y terapia fotodinámica fue tóxico para las células THP-1 (CC 50 0,00032 ±0,00002 mM) y para los promastigotes de L. (L .) infantum (IC 50 0,003±0,0001 mM) y L. ( V .) panamensis (CI 50 0,024±0,0001 mM). Conclusiones. A pesar de la ‘fotoactividad´ del tratamiento con protoporfirina IX en promastigotes y de su producción después del tratamiento con ácido aminolevulínico y metil-5-aminolevulinato en las células infectadas con Leishmania , no se observó daño en los amastigotes presentes en las células de L. ( L .) infantum o L . ( V .) panamensis .


Subject(s)
Humans , Aminolevulinic Acid/analogs & derivatives , Aminolevulinic Acid/pharmacology , Leishmania guyanensis/drug effects , Leishmania infantum/drug effects , Monocytes/drug effects , Photochemotherapy , Photosensitizing Agents/pharmacology , Protoporphyrins/analysis , Subcellular Fractions/drug effects , Aminolevulinic Acid/radiation effects , Amphotericin B/pharmacology , Cell Line, Tumor , Colorimetry , Leukemia, Monocytic, Acute/pathology , Lysosomes/chemistry , Microscopy, Fluorescence , Mitochondria/chemistry , Monocytes/parasitology , Monocytes/ultrastructure , Photosensitizing Agents/radiation effects , Species Specificity , Subcellular Fractions/chemistry
6.
Immunopharmacol Immunotoxicol ; 35(4): 478-86, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23855487

ABSTRACT

CONTEXT: We have previously reported that benznidazole (BZL), known for its trypanocidal action, has anti-proliferative activity against different cell lines like HeLa and Raw 264.7 among others. At the moment, it has not been reported if the anti-proliferative effect of BZL is similar for non-adherent hematopoietic cells like was reported for adherent cancer cell lines. OBJECTIVE: We aimed to investigate the efficacy of BZL on the growth of the leukemic cell lines THP-1 and OCI/AML3. MATERIALS AND METHODS: We evaluated cell proliferation by [³H]-thymidine incorporation and MTT reduction as well as cell death by lactate dehydrogenase (LDH) activity. We assessed apoptosis by flow cytometry for detection of annexin V-positive and propidium iodide-negative cells, along with nuclear morphology by diamidino-2-phenolindole (DAPI) staining. Western blot studies were performed to evaluate changes in cell cycle proteins in BZL-treated cells. RESULTS: BZL significantly reduced proliferation of both cell lines without inducing cell death. Likewise it produced no significant differences in apoptosis between treated cells and controls. In addition, flow cytometry analysis indicated that BZL caused a larger number of THP-1 cells in G0/G1 phase and a smaller number of cells in S phase than controls. This was accompanied with an increase in the expression of the CDK inhibitor p27 and of cyclin D1, with no significant differences in the protein levels of CDK1, CDK2, CDK4, cyclins E, A and B as compared to controls. CONCLUSION: BZL inhibits the proliferation of leukemic non-adherent cells by controlling cell cycle at G0/G1 cell phase through up-regulation of p27.


Subject(s)
Cell Cycle Checkpoints/drug effects , Leukemia, Monocytic, Acute/metabolism , Nitroimidazoles/pharmacology , Trypanocidal Agents/pharmacology , Cell Death/drug effects , Cyclin-Dependent Kinase Inhibitor p27/biosynthesis , Cyclin-Dependent Kinases/biosynthesis , Cyclins/biosynthesis , Gene Expression Regulation, Leukemic/drug effects , HeLa Cells , Humans , Leukemia, Monocytic, Acute/pathology , Neoplasm Proteins/biosynthesis
7.
Am J Hematol ; 87(9): 890-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22685031

ABSTRACT

Although rarely, switches between lymphoid and myeloid lineages may occur during treatment of acute leukemias (AL). Correct diagnosis relies upon confirmation by immunophenotyping of the lineage conversion and certification that the same cytogenetic/molecular alterations remain despite the phenotypic changes. From a total of 1,482 AL pediatric patients, we report nine cases of lineage conversion (0.6%), seven from lymphoid (four Pro-B, two Pre-B, one Common) to myelo-monocytic, and two from myeloid (bilineal, with myeloid predominance) to Pro-B. Eight patients were infants. Switches were suggested by morphology and confirmed with a median of 15 days (range: 8 days-6 months) from initiation of therapy. Of note, in five cases switches occurred before day 15. Stability of the clonal abnormalities was assessed by cytogenetic, RT-PCR/Ig-TCR rearrangement studies in all patients. Abnormalities in 11q23/MLL gene were detected in seven cases. Treatment schedules were ALL (two pts), Interfant-99 (five pts) and AML (two pts) protocols. Despite changing chemotherapy according to the new lineage, all patients died. Our findings support the association of lineage switches with MLL gene alterations and the involvement of a common lymphoid B-myeloid precursor. New therapies should be designed to address these rare cases. Possible mechanisms implicated are discussed.


Subject(s)
Cell Lineage/genetics , Leukemia, Monocytic, Acute/genetics , Leukemia, Monocytic, Acute/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Adolescent , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Chromosomes, Human, Pair 11/genetics , Cytogenetic Analysis , Gene Rearrangement, T-Lymphocyte/genetics , Histocytochemistry , Histone-Lysine N-Methyltransferase , Humans , Immunophenotyping , Infant , Infant, Newborn , Leukemia, Monocytic, Acute/drug therapy , Leukemia, Monocytic, Acute/mortality , Myeloid-Lymphoid Leukemia Protein/genetics , Oncogene Proteins, Fusion/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Reverse Transcriptase Polymerase Chain Reaction , Translocation, Genetic , Treatment Outcome
10.
Exp Parasitol ; 122(4): 353-6, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19460378

ABSTRACT

This study, undertaken to compare the susceptibility of THP-1 cells and murine peritoneal macrophages to Leishmania peruviana amastigotes, obtained THP-1 infection with 10 parasites/cell compared to 2 parasites/murine macrophage. The parasite burden was maximal at 72 h post-infection (h.p.i.) for THP-1 cells, while it was still increasing at 120 h.p.i. for murine macrophages. Since in both cases the infection with L. peruviana affected cell viability, we recommend evaluating any leishmanicidal activity at 72 h.p.i. Amphotericin B reduced Leishmania infection by 50% at concentrations of 0.1 microM in THP-1 and murine macrophages at 72 h.p.i. Our results demonstrate that amastigotes of L. peruviana can infect THP-1 cells and murine macrophages and indicate the suitability of this model to screen compounds for leishmanicidal activity.


Subject(s)
Amphotericin B/pharmacology , Antiprotozoal Agents/pharmacology , Leishmania braziliensis/pathogenicity , Macrophages, Peritoneal/parasitology , Monocytes/parasitology , Amphotericin B/toxicity , Animals , Antiprotozoal Agents/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Female , Humans , Inhibitory Concentration 50 , Leishmania braziliensis/drug effects , Leukemia, Monocytic, Acute/pathology , Macrophages, Peritoneal/drug effects , Mice , Monocytes/drug effects
11.
P R Health Sci J ; 27(3): 256-8, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18782972

ABSTRACT

Aleukemic leukemia cutis is an extremely rare clinical presentation in patients who eventually develop acute leukemia, usually of monocytic lineage. This condition is associated with a very poor prognosis and is often difficult to diagnose. We report a case of a 33 years old female with leukemia cutis preceding the onset of acute monocytic leukemia by four months. The patient received induction and consolidation chemotherapy followed by allogeneic bone marrow transplant and has been free of disease for six years. To our knowledge, this is the first documented case in Puerto Rico with the diagnosis of leukemia cutis preceding acute monocytic leukemia.


Subject(s)
Leukemia, Monocytic, Acute/pathology , Leukemic Infiltration , Skin/pathology , Female , Humans , Leukemia, Monocytic, Acute/therapy , Middle Aged
12.
Leuk Res ; 29(12): 1465-7, 2005 Dec.
Article in English | MEDLINE | ID: mdl-15964069

ABSTRACT

Patients with 1q duplication have demonstrated a wide range of multiple congenital abnormalities. Alterations involving this chromosomal region have being described in hematopoietic malignancies and a series of candidate genes that may be associated with neoplasias have been mapped in this region. We describe a case of partial trisomy 1q "syndrome" and acute monocytic leukemia. Cytogenetic study of the bone marrow cells by GTG-banding and spectral karyotyping (SKY) showed dup(1)(q23q44) in all cells analyzed. The dismorphological features with the dup(1q) suggest a constitutional chromosome alteration and the first, in our knowledge, association of a trisomy 1q "syndrome" with AML.


Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 1 , Leukemia, Monocytic, Acute/genetics , Trisomy , Abnormalities, Multiple/pathology , Bone Marrow/pathology , Chromosome Banding/methods , Female , Humans , Infant , Leukemia, Monocytic, Acute/pathology , Spectral Karyotyping
13.
Chemotherapy ; 50(5): 221-8, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15528887

ABSTRACT

BACKGROUND: Apoptosis is an essential form of cell death, the failure of which can lead to cancer development. Cancer including leukemia is usually treated with chemotherapeutic drugs that can be effective, but frequently problems are encountered that impair the success of the treatment. Butyrate is a short-chain fatty acid that can have many effects on different cells, including apoptosis. METHODS: The effect of a combination treatment with butyrate and antineoplastic agents Ara-C, etoposide and vincristine is evaluate on the leukemic cell line THP-1. RESULTS: We show that butyrate increased apoptosis induced by the three agents as seen by measurement of DNA content, annexin exposure and morphological characteristics. We also demonstrate that the process of apoptosis induced by butyrate and chemotherapeutic drugs involves the participation of caspases and induced activation of caspase-3, -8 and -9. CONCLUSIONS: We believe that butyrate could be a promising therapeutic agent for the treatment of leukemia in combination with other antineoplastic drugs.


Subject(s)
Antineoplastic Agents/pharmacology , Butyrates/pharmacology , Drug Synergism , Leukemia, Monocytic, Acute/drug therapy , Leukemia, Monocytic, Acute/pathology , Amino Acid Chloromethyl Ketones/pharmacology , Amino Acid Chloromethyl Ketones/therapeutic use , Antineoplastic Agents/classification , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Apoptosis/physiology , Blotting, Western , Butyrates/chemistry , Butyrates/therapeutic use , Caspase Inhibitors , Caspases/metabolism , Caspases/therapeutic use , Cell Line, Tumor , Cytarabine/pharmacology , Cytarabine/therapeutic use , DNA Replication/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor/methods , Drug Therapy, Combination , Etoposide/pharmacology , Etoposide/therapeutic use , Humans , Leukemia, Monocytic, Acute/metabolism , Vincristine/pharmacology , Vincristine/therapeutic use
14.
Hematol J ; 4(1): 26-30, 2003.
Article in English | MEDLINE | ID: mdl-12692517

ABSTRACT

INTRODUCTION: Classically, the monocytic component of acute myelomonocytic (FAB-M4) and acute monocytic/monoblastic (FAB-M5) leukemias is demonstrated by nonspecific esterase positivity in cytochemical stainings. We have previously demonstrated that non-specific esterases from normal monocytes can be determined by a chemiluminescent method. In the present study, we investigated whether this assay can also determine the monocytic component of FAB-M4 and FAB-M5 and distinguish these acute myeloid leukemia (AML) categories. MATERIALS AND METHODS: Bone marrow samples were obtained from 66 patients with AML (M0, two cases; M1, 12 cases; M2, 13 cases; M3, 10 cases; M4, 11 cases; M5, 12 cases; M6, two cases; M7, four cases). Cells were incubated with a standard reaction mixture and chemiluminescence was measured for 10 min. Two parameters were assessed, the peak (PLE) and the integrated light emission (ILE). RESULTS: Both PLE and ILE were higher in FAB-M4 and FAB-M5 subtypes compared to other AML subtypes (P<0.001). In addition, the classification of AML cases into FAB-M4, FAB-M5 and nonmonocytic subtypes based on ILE analysis was concordant with alpha-naphthyl acetate esterase (ANAE) in 97% of cases (kappa coefficient 0.94, P<0.001). CONCLUSIONS: These findings indicate that this chemiluminescent assay was able to determine the monocytic component of FAB-M4 and FAB-M5 cells, and the classification of AML subtypes based on chemiluminescent analysis strongly agreed with the cytochemical ANAE-staining. In conclusion, this chemiluminescent assay is a simple, fast and objective method, which may be useful as an alternative tool in the differential diagnosis of AML subtypes.


Subject(s)
Bone Marrow/pathology , Leukemia, Monocytic, Acute/pathology , Leukemia, Myelomonocytic, Acute/pathology , Luminescent Measurements , Monocytes/pathology , Neoplastic Stem Cells/pathology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Benzoates/metabolism , Carboxylesterase , Carboxylic Ester Hydrolases/analysis , Child , Child, Preschool , Cryopreservation , Diagnosis, Differential , Female , Horseradish Peroxidase/metabolism , Humans , Leukemia, Monocytic, Acute/diagnosis , Leukemia, Monocytic, Acute/enzymology , Leukemia, Myeloid/pathology , Leukemia, Myelomonocytic, Acute/diagnosis , Leukemia, Myelomonocytic, Acute/enzymology , Male , Middle Aged , Monocytes/enzymology , Neoplasm Proteins/analysis , Neoplastic Stem Cells/enzymology , Sodium Fluoride/pharmacology
15.
Cancer Res ; 61(16): 6281-9, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11507083

ABSTRACT

Cell-cell interaction is important in the expansion of leukemic cells and of solid tumors. Steel factor (SF) or Kit ligand is produced as a membrane-bound form (mSF) and a soluble form. Because both primary gynecological tumors and primary leukemic cells from patients with acute myeloblastic leukemia (AML) have been shown to coexpress c-Kit and SF, we addressed the question of whether mSF could contribute to cell interaction in these cancers. Investigations on primary cervical carcinomas have been hindered by the fact that the cells do not grow in culture. We report herein the establishment of two cervical carcinoma cell lines, CALO and INBL, that reproduce the pattern of SF/c-Kit expression observed in primary tumor samples. In addition, these cells exhibit marked density-dependent growth much in the same way as AML blasts. Using an antisense strategy with phosphorothioate-modified oligonucleotides that specifically target SF without affecting other surface markers, we provide direct evidence for a role of mSF and c-Kit in cell interaction and cell survival in these gynecological tumor cell lines as well as in primary AML blasts. Finally, our study defines the importance of juxtacrine stimulation, which may be as important, if not more, than autocrine stimulation in cancers.


Subject(s)
Cell Communication/physiology , Leukemia, Myeloid/pathology , Proto-Oncogene Proteins c-kit/physiology , Stem Cell Factor/physiology , Uterine Cervical Neoplasms/pathology , 3T3 Cells , Acute Disease , Animals , Cell Count , Cell Division/physiology , Cell Survival/physiology , Chlorocebus aethiops , Female , HeLa Cells , Humans , Leukemia, Monocytic, Acute/genetics , Leukemia, Monocytic, Acute/metabolism , Leukemia, Monocytic, Acute/pathology , Leukemia, Myeloid/metabolism , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Leukemia, Myelomonocytic, Acute/genetics , Leukemia, Myelomonocytic, Acute/metabolism , Leukemia, Myelomonocytic, Acute/pathology , Mice , Oligonucleotides, Antisense/genetics , Oligonucleotides, Antisense/pharmacology , Proto-Oncogene Proteins c-kit/biosynthesis , Proto-Oncogene Proteins c-kit/genetics , Stem Cell Factor/antagonists & inhibitors , Stem Cell Factor/biosynthesis , Stem Cell Factor/genetics , Thionucleotides/genetics , Thionucleotides/pharmacology , Tumor Cells, Cultured
16.
J Immunol ; 161(9): 4960-7, 1998 Nov 01.
Article in English | MEDLINE | ID: mdl-9794432

ABSTRACT

We investigated the effects of dexamethasone or indomethacin on the NADPH oxidase activity, cytochrome b558 content, and expression of genes encoding the components gp91-phox and p47-phox of the NADPH oxidase system in the human monocytic THP-1 cell line, differentiated with IFN-gamma and TNF-alpha, alone or in combination, for up to 7 days. IFN-gamma and TNF-alpha, alone or in combination, caused a significant up-regulation of the NADPH oxidase system as reflected by an enhancement of the PMA-stimulated superoxide release, cytochrome b558 content, and expression of gp91-phox and p47-phox genes on both days 2 and 7 of cell culture. Noteworthy was the tremendous synergism between IFN-gamma and TNF-alpha for all studied parameters. Dexamethasone down-regulated the NADPH oxidase system of cytokine-differentiated THP-1 cells as assessed by an inhibition on the PMA-stimulated superoxide release, cytochrome b558 content, and expression of the gp91-phox and p47-phox genes. The nuclear run-on assays indicated that dexamethasone down-regulated the NADPH oxidase system at least in part by inhibiting the transcription of gp91-phox and p47-phox genes. Indomethacin inhibited only the PMA-stimulated superoxide release of THP-1 cells differentiated with IFN-gamma and TNF-alpha during 7 days. None of the other parameters was affected by indomethacin. We conclude that dexamethasone down-regulates the NADPH oxidase system at least in part by inhibiting the expression of genes encoding the gp91-phox and p47-phox components of the NADPH oxidase system.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Enzyme Inhibitors/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Indomethacin/pharmacology , Membrane Glycoproteins/biosynthesis , Monocytes/drug effects , NADPH Oxidases/antagonists & inhibitors , Phosphoproteins/biosynthesis , Cells, Cultured , Cytochrome b Group/biosynthesis , Cytochrome b Group/genetics , Humans , Interferon-gamma/pharmacology , Leukemia, Monocytic, Acute/pathology , Membrane Glycoproteins/genetics , Monocytes/enzymology , NADPH Oxidase 2 , NADPH Oxidases/biosynthesis , NADPH Oxidases/genetics , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Phosphoproteins/genetics , Superoxides/metabolism , Tetradecanoylphorbol Acetate/pharmacology , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/pharmacology
17.
J Pediatr ; 131(2): 300-3, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9290620

ABSTRACT

Most patients with congenital leukemia do not survive past infancy despite aggressive chemotherapy. We describe three patients with congenital leukemia who have undergone prolonged periods of spontaneous remission. Our experience suggests that some patients with congenital leukemia may benefit from initial conservative management without chemotherapy. We summarize the clinical presentations of these patients and review the literature.


Subject(s)
Leukemia, Monocytic, Acute/congenital , Leukemia, Myeloid/congenital , Leukemia, Myelomonocytic, Acute/congenital , Neoplasm Regression, Spontaneous , Skin Neoplasms/congenital , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biopsy , Female , Follow-Up Studies , Humans , Infant, Newborn , Leukemia, Monocytic, Acute/drug therapy , Leukemia, Monocytic, Acute/pathology , Leukemia, Myeloid/pathology , Leukemia, Myelomonocytic, Acute/drug therapy , Leukemia, Myelomonocytic, Acute/pathology , Male , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Remission Induction , Skin Neoplasms/pathology
18.
Rev Invest Clin ; 49(4): 295-8, 1997.
Article in Spanish | MEDLINE | ID: mdl-9707995

ABSTRACT

Bone marrow necrosis (BMN) is mostly diagnosed at postmortem examination. It has been observed in association with acute leukemia and other malignant diseases. We report here BMN in two patients with acute myeloid leukemia (AML) and one with acute lymphocytic leukemia (ALL) in whom the diagnosis was made while alive. Two patients died because of intracranial bleeding. One with AML (M5) developed BMN one week after he was treated with a second course of chemotherapy: he had a complete recovery and remains in remission almost five years after the diagnosis. We conclude that antemortem diagnosis of BMN is technically difficult, but as it is not always associated to a fatal prognosis, an early diagnosis and vigorous supportive therapy should be attempted.


Subject(s)
Bone Marrow/pathology , Leukemia, Monocytic, Acute/pathology , Leukemia, Promyelocytic, Acute/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Examination , Cerebral Hemorrhage/etiology , Fatal Outcome , Female , Humans , Leukemia, Monocytic, Acute/drug therapy , Male , Middle Aged , Necrosis , Pain/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Remission Induction
19.
Leuk Lymphoma ; 22(1-2): 163-71,follow.186,color plate XIV-V, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8724544

ABSTRACT

We studied the effect of TPA, G-CSF, GM-CSF, conditioned medium from 5637 cells (CM5637) and IL-4 on U-937 cell line proliferation and differentiation. Flow cytometry analysis showed that the expression of the CD14 cell surface antigen, initially detected in 90% of the cells, decreased when the cells were cultured with either G-CSF, GM-CSF, CM5637, or IL-4. The CD11c expression only decreased by exposure to GM-CSF and IL-4. The cells also showed a decrease in alpha-naphthylesterase (alpha-NAE) activity and an increase in peroxidase (Px) activity in the GM-CSF supplemented cultures. Remarkable changes in cell morphology were also observed. IL-4 induced morphologic features resembling histiocytic-like cells positive for the expression of alpha-NAE and negative for Px. GM-CSF induced cells with pseudopods, negative for alpha-NAE expression and positive for Px. TPA effect on U-937 cells was similar to that observed with GM-CSF. No proliferative response was detected with any of the factors assayed. These results suggest that GM-CSF and IL-4 can promote distinct changes in the differentiative pathway of U-937 cells, as evidenced by the marked morphological, immunological and cytochemical changes observed in the cell cultures.


Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacology , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Interleukin-4/pharmacology , Leukemia, Monocytic, Acute/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Monocytes/drug effects , Neoplastic Stem Cells/drug effects , Biomarkers , Carcinoma/metabolism , Cell Differentiation/drug effects , Culture Media, Conditioned/pharmacology , Cytokines/metabolism , Cytokines/pharmacology , Enzyme Induction/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Integrin alphaXbeta2/biosynthesis , Lipopolysaccharide Receptors/biosynthesis , Monocytes/metabolism , Monocytes/pathology , Naphthol AS D Esterase/biosynthesis , Neoplasm Proteins/biosynthesis , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Peroxidase/biosynthesis , Recombinant Proteins/pharmacology , Tetradecanoylphorbol Acetate/pharmacology , Tumor Cells, Cultured , Urinary Bladder Neoplasms/metabolism
20.
J Pediatr ; 112(1): 18-22, 1988 Jan.
Article in English | MEDLINE | ID: mdl-2961859

ABSTRACT

Two infants with Down syndrome had transient myeloproliferative disorder (TMD) during the neonatal period and subsequently acute nonlymphoblastic leukemia (ANLL). Histochemically, the blast cells in TMD were indistinguishable from those in ANLL. Only the constitutional chromosome (trisomy 21) was found in TMD, whereas new cytogenetic abnormalities emerged in ANLL. A mixed growth pattern in stem cell cultures during TMD suggested the existence of an abnormal clone that might be responsible for the evolution into ANLL at a later date. Serial cytogenetic studies and culture studies of peripheral blood cells may help to understand the pathophysiology and risk of ANLL in patients with TMD.


Subject(s)
Down Syndrome/blood , Leukemia/blood , Leukemoid Reaction/blood , Acute Disease , Blood Cell Count , Bone Marrow Examination , Colony-Forming Units Assay , Down Syndrome/pathology , Hematopoietic Stem Cells , Humans , Infant, Newborn , Leukemia/pathology , Leukemia, Monocytic, Acute/blood , Leukemia, Monocytic, Acute/pathology , Leukemoid Reaction/pathology , Male
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