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1.
Int J Hematol ; 119(4): 465-471, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38424413

RESUMO

While our understanding of the molecular basis of mixed phenotype acute leukemia (MPAL) has progressed over the decades, our knowledge is limited and the prognosis remains poor. Investigating cases of familial leukemia can provide insights into the role of genetic and environmental factors in leukemogenesis. Although familial cases and associated mutations have been identified in some leukemias, familial occurrence of MPAL has never been reported. Here, we report the first cases of MPAL in a family. A 68-year-old woman was diagnosed with MPAL and received haploidentical stem cell transplantation from her 44-year-old son. In four years, the son himself developed MPAL. Both cases exhibited similar characteristics such as biphenotypic leukemia with B/myeloid cell antigens, Philadelphia translocation (BCR-ABL1 mutation), and response to acute lymphoblastic leukemia-type chemotherapy. These similarities suggest the presence of hereditary factors contributing to the development of MPAL. Targeted sequencing identified shared germline variants in these cases; however, in silico analyses did not strongly support their pathogenicity. Intriguingly, when the son developed MPAL, the mother did not develop donor-derived leukemia and remained in remission. Our cases provide valuable insights to guide future research on familial MPAL.


Assuntos
Leucemia Aguda Bifenotípica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Feminino , Idoso , Adulto , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Doença Aguda , Fenótipo , Células Germinativas , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/terapia , Leucemia Aguda Bifenotípica/diagnóstico
2.
Indian J Pathol Microbiol ; 67(1): 121-127, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358200

RESUMO

Background: : Acute leukemia of ambiguous lineage (ALAL) is a heterogeneous group of rare leukemias that lacks definite evidence of differentiation along one lineage. It includes acute undifferentiated leukemia and mixed-phenotype acute Leukaemia (MPAL). Aims: The present study highlighted the clinicohematological and immunophenotypic profile of ALAL cases diagnosed in the tertiary care centre of western India. Study Design: Retrospective observational study. Methods and Materials: Patients diagnosed with acute leukemia, preferably their bone marrow aspirate samples, were collected in ethylene diamine tetra-acetic acid-vial. The immunophenotypic study was done using the Fluorescence Activated Cell Sorting (FACS) Canto Eight color flow cytometer and a broad panel of monoclonal antibodies. The patients were diagnosed for ALAL, based on the World Health Organization (WHO) 2017 classification. Statistical Analysis Used: Descriptive statistics with categorical and continuous variables. Results: Overall incidence of ALAL was about 2.1%, and singly MPAL and AUL were 1.8%, and 0.3%, in frequency, respectively. The age range was 4 to 57 (median age 21 years), of which 11 (57.9%) were adults and eight were children (42.1%). There was male predominance with Male: Female ratio of 5.3:1. On immunophenotyping, B/myeloid MPAL (42.1%) was the commonest among the ALAL. Translocation t(9;22) was the most common cytogenetic abnormality found mainly in B/myeloid MPAL. Two cases were of chronic myeloid leukemia in a mixed phenotypic blast crisis. Over all prognosis of ALAL was poor. Conclusion: ALAL is overall associated with poor prognosis as both their diagnosis and treatment decisions are difficult owing to the lack of optimum treatment data and the rarity of the disease. Hence, A careful diagnosis with the help of immunophenotyping is crucial.


Assuntos
Leucemia Aguda Bifenotípica , Leucemia Mieloide Aguda , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Doença Aguda , Imunofenotipagem , Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/terapia , Prognóstico , Centros de Atenção Terciária , Pré-Escolar , Adolescente , Pessoa de Meia-Idade
3.
Clin Lab ; 69(4)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37057942

RESUMO

BACKGROUND: The aim of the study was to improve the understanding of complex karyotype acute mixed cell leukemia containing pseudo Chediak-Higashi granules. METHODS: A case of acute mixed cell leukemia resembling AML1-ETO positive acute myeloid leukemia was reported. The results of morphological, immunophenotypic, and cytogenetic tests were analyzed by reviewing relevant literature. RESULTS: The patient was a young boy with clinical manifestations of recurrent fever. Bone marrow smear: Granulocyte system hyperplasia is obvious, visible at each stage, primitive cells account for 12%. These cells are large in volume, mostly round or class round, with abundant cell mass, stained gray blue, unbalanced development of some nuclear plasma, abnormal cytoplasmic staining, and visible "sunrise red" -like changes. Typical Auer bodies, pseudo Chadiak-Higashi granules and phagocytic erythroid substances were observed. The nuclei are irregular in shape, distorted and depressed, with fine chromatin and prominent large nucleoli. Bone marrow was extracted 3 days later, the bone marrow smear showed 65% primitive cells. The morphology of primitive cells was similar to that of 3 days ago. The results of flow cytometry showed that the primary/naive T cells in the samples possessed nuclear cells. Flow cytometry showed two groups of abnormal cells. One group accounted for 3.87% of nuclear cells and was a primitive/naive T-cell phenotype, mainly expressing: CD34+, CD7+, CD5+, CD2dim+, MPO-, CCD3 + part, CD3-, CD4-, CD8 -, CD117 -, CD13-, CD33-, HLA - DR -, CD10-, CD11b-, CD56-. The other group which accounted for 79.8% of the nuclear cells was monocyte phenotype, mainly expressing: CD34-, CD117-, CD13+ small amount, CD33+, HLA-DR-, CD11b+, CD14+, CD15+, CD36+, CD56+, CD64+, CD4+, CD85J+, CD85K + part. It matched the immunophenotype of acute mixed cell leukemia (T/MMPAL). Immunophenotypic leukemia-related fusion genes were negative, and karyotype analysis results were 45, XY, T (11; 12)(p13; Q13), -12-17, + mar [12]/90 < n > 4, idem x 2 [6]/46, XY. Combined with the above results, acute mixed cell leukemia was diagnosed. CONCLUSIONS: The flow cytometry is the gold standard in the diagnosis of acute mixed cell leukemia. The diagnosis of acute mixed cell leukemia requires the combination of clinical manifestations, cellular morphology, immunology, cytogenetics and molecular biology, and the comprehensive diagnosis efficiency is obviously better than that of morphology.


Assuntos
Leucemia Aguda Bifenotípica , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Antígenos HLA-DR/análise , Medula Óssea/química , Fenótipo , Imunofenotipagem , Proteína 1 Parceira de Translocação de RUNX1/genética , Proteínas de Fusão Oncogênica/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética
4.
Haematologica ; 108(5): 1244-1258, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36325888

RESUMO

Persistence of residual disease after induction chemotherapy is a strong predictor of relapse in acute lymphoblastic leukemia (ALL). The bone marrow microenvironment may support escape from treatment. Using three-dimensional fluorescence imaging of ten primary ALL xenografts we identified sites of predilection in the bone marrow for resistance to induction with dexamethasone, vincristine and doxorubicin. We detected B-cell precursor ALL cells predominantly in the perisinusoidal space at early engraftment and after chemotherapy. The spatial distribution of T-ALL cells was more widespread with contacts to endosteum, nestin+ pericytes and sinusoids. Dispersion of T-ALL cells in the bone marrow increased under chemotherapeutic pressure. A subset of slowly dividing ALL cells was transiently detected upon shortterm chemotherapy, but not at residual disease after chemotherapy, challenging the notion that ALL cells escape treatment by direct induction of a dormant state in the niche. These lineage-dependent differences point to niche interactions that may be more specifically exploitable to improve treatment.


Assuntos
Linfoma de Burkitt , Leucemia Aguda Bifenotípica , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Medula Óssea , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Microambiente Tumoral
6.
Am J Clin Pathol ; 158(1): 27-34, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35775438

RESUMO

OBJECTIVES: Classification of acute leukemia involves assigning lineage by resemblance to normal progenitor cells. This approach provides descriptive information about the blast cells that is useful for disease monitoring, provides clues to pathogenesis, and can help clinicians select effective chemotherapeutic regimens. Acute leukemias of ambiguous lineage (ALALs) are those leukemias that either fail to show evidence of myeloid, B-, or T-lymphoid lineage commitment or show evidence of commitment to more than 1 lineage. The different treatment regimens for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) make ALAL a challenge both diagnostically and therapeutically. METHODS: Current classification criteria have reduced the reported incidence of mixed-lineage leukemias by emphasizing fewer markers and categorizing some biphenotypic leukemias with recurrent cytogenetic abnormalities as other entities. Several recent studies have explored the genomic and epigenetic landscape of mixed-phenotype acute leukemia (MPAL) and have suggested a further refinement of the World Health Organization classification to emphasize the genomic heterogeneity of MPAL. RESULTS: Genomic and expression profile data for MPAL reveal mutations commonly seen in both AML and ALL, with T-/myeloid MPAL showing overlapping features with early T-cell precursor lymphoblastic leukemia. CONCLUSIONS: Our review aimed to discuss the diagnostic challenges, recent genomic studies, and therapeutic strategies in this poorly understood disease.


Assuntos
Leucemia Aguda Bifenotípica , Leucemia Mieloide Aguda , Leucemia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Doença Aguda , Humanos , Imunofenotipagem , Leucemia/diagnóstico , Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/patologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico
7.
Blood ; 139(3): 313-315, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35050331
10.
Haematologica ; 107(4): 803-815, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33910331

RESUMO

Although great advances have been made in understanding the pathobiology of mixed lineage leukemia-rearranged (MLL-r) leukemias, therapies for this leukemia have remained limited, and clinical outcomes remain bleak. In order to identify novel targets for immunotherapy treatments, we compiled a lineage-independent MLL-r leukemia gene signature using publicly available data sets. Data from large leukemia repositories were filtered through the in silico human surfaceome, providing a list of highly predicted cell surface proteins overexpressed in MLL-r leukemias. LAMP5, a lysosomal associated membrane protein, is expressed highly and specifically in MLL-r leukemia. We found that LAMP5 is a direct target of the oncogenic MLL-fusion protein. LAMP5 depletion significantly inhibited leukemia cell growth in vitro and in vivo. Functional studies showed that LAMP-5 is a novel modulator of innate-immune pathways in MLL-r leukemias. Downregulation of LAMP5 led to inhibition of NF-kB signaling and increased activation of type-1 interferon signaling downstream of Toll-like receptor/interleukin 1 receptor activation. These effects were attributable to the critical role of LAMP-5 in transferring the signal flux from interferon signaling endosomes to pro-inflammatory signaling endosomes. Depletion of IRF7 was able to partially rescue the cell growth inhibition upon LAMP5 downregulation. Lastly, LAMP-5 was readily detected on the surface of MLL-r leukemia cells. Targeting surface LAMP-5 using an antibody-drug conjugate leads to significant cell viability decrease specifically in MLL-r leukemias. Overall, based on the limited expression throughout human tissues, we postulate that LAMP-5 could potentially serve as an immunotherapeutic target with a wide therapeutic window to treat MLL-r leukemias.


Assuntos
Leucemia Aguda Bifenotípica , Leucemia , Histona-Lisina N-Metiltransferase/genética , Humanos , Imunoterapia , Leucemia/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo
11.
J Mol Biol ; 434(1): 167117, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174329

RESUMO

AF9 (MLLT3) and ENL (MLLT1) are members of the YEATS family (named after the five proteins first shown to contain this domain: Yaf9, ENL, AF9, Taf14, Sas5) defined by the presence of a YEATS domain. The YEATS domain is an epigenetic reader that binds to acetylated and crotonylated lysines, unlike the bromodomain which can only bind to acetylated lysines. All members of this family have been shown to be components of various complexes with roles in chromatin remodeling, histone modification, histone variant deposition, and transcriptional regulation. MLLT3 is a critical regulator of hematopoiesis with a role in maintaining the hematopoietic stem or progenitor cell (HSPC) population. Approximately 10% of acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients harbor a translocation involving MLL (mixed lineage leukemia). In the context of MLL fusion patients with AML and ALL, MLL-AF9 and MLL-ENL fusions are observed in 34 and 31% of the patients, respectively. The intrinsically disordered C-terminal domain of MLLT3 (AHD, ANC1 homology domain) undergoes coupled binding and folding upon interaction with partner proteins AF4, DOT1L, BCOR, and CBX8. Backbone dynamics studies of the complexes suggest a role for dynamics in function. Inhibitors of the interaction of the intrinsically disordered AHD with partner proteins have been described, highlighting the feasibility of targeting intrinsically disordered regions. MLLT1 undergoes phase separation to enhance recruitment of the super elongation complex (SEC) and drive transcription. Mutations in MLLT1 observed in Wilms tumor patients enhance phase separation and transcription to drive an aberrant gene expression program.


Assuntos
Hematopoese/fisiologia , Neoplasias Renais/genética , Proteínas de Neoplasias/fisiologia , Proteínas Nucleares/fisiologia , Fatores de Transcrição/fisiologia , Tumor de Wilms/genética , Fusão Gênica , Humanos , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/metabolismo , Leucemia Aguda Bifenotípica/genética , Mutação , Proteínas de Neoplasias/química , Proteínas Nucleares/química , Domínios e Motivos de Interação entre Proteínas , Fatores de Transcrição/química
12.
Eur J Haematol ; 108(2): 163-165, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34653270

RESUMO

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia where blasts present phenotypes from more than one lineage. A poor prognostic has been associated with this disease, and limited data are currently available to guide the choice of therapy. Regarding FLT3-positive MPAL, only one case treated with midostaurin has been published to date. Here, we report the successful use of midostaurin to treat three FLT3-positive MPAL T/myeloid and B/myeloid patients. Midostaurin was successfully added to intensive induction (two patients) and consolidation chemotherapy (three patients) without significant adverse events requiring a dose adjustment or discontinuation. The therapy received resulted in complete remission for two patients and complete remission with an incomplete hematologic recovery for the third. All patients proceeded to HSCT and stayed in remission after an extended follow-up respectively at 28, 31, and 11 months later. These results suggest that the addition of midostaurin during induction and consolidation therapy may represent a treatment option for FLT3-positive MPAL.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Aguda Bifenotípica/tratamento farmacológico , Leucemia Aguda Bifenotípica/genética , Mutação , Estaurosporina/análogos & derivados , Tirosina Quinase 3 Semelhante a fms , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais , Linhagem da Célula/genética , Feminino , Humanos , Leucemia Aguda Bifenotípica/diagnóstico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Fenótipo , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estaurosporina/administração & dosagem , Estaurosporina/efeitos adversos , Estaurosporina/uso terapêutico , Resultado do Tratamento
13.
Theranostics ; 11(19): 9519-9537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646384

RESUMO

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed-lineage leukemia gene rearrangement (MLL-r) is a poor-prognosis subtype for which additional therapeutic targets are urgently needed. Currently no multi-omics data set for primary MLL r patient cells exists that integrates transcriptomics, proteomics and glycomics to gain an inclusive picture of theranostic targets. Methods: We have integrated transcriptomics, proteomics and glycomics to i) obtain the first inclusive picture of primary patient BCP-ALL cells and identify molecular signatures that distinguish leukemic from normal precursor B-cells and ii) better understand the benefits and limitations of the applied technologies to deliver deep molecular sequence data across major cellular biopolymers. Results: MLL-r cells feature an extensive remodeling of their glycocalyx, with increased levels of Core 2-type O-glycans and complex N-glycans as well as significant changes in sialylation and fucosylation. Notably, glycosaminoglycan remodeling from chondroitin sulfate to heparan sulfate was observed. A survival screen, to determine if glycan remodeling enzymes are redundant, identified MGAT1 and NGLY1, essential components of the N-glycosylation/degradation pathway, as highly relevant within this in vitro screening. OGT and OGA, unique enzymes that regulate intracellular O-GlcNAcylation, were also indispensable. Transcriptomics and proteomics further identified Fes and GALNT7-mediated glycosylation as possible therapeutic targets. While there is overall good correlation between transcriptomics and proteomics data, we demonstrate that a systematic combined multi-omics approach delivers important diagnostic information that is missed when applying a single omics technology. Conclusions: Apart from confirming well-known MLL-r BCP-ALL glycoprotein markers, our integrated multi-omics workflow discovered previously unidentified diagnostic/therapeutic protein targets.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Linhagem Celular Tumoral , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Leucêmica da Expressão Gênica/genética , Rearranjo Gênico/genética , Glicômica/métodos , Histona-Lisina N-Metiltransferase/genética , Humanos , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/metabolismo , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteômica/métodos , Transcriptoma/genética
14.
Rinsho Ketsueki ; 62(7): 717-720, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34349053

RESUMO

This study reports a case of a 49-year-old woman having B-cell acute lymphoblastic leukemia with glycophorin A, a representative erythroid marker, expression. According to the WHO criteria for mixed phenotype acute leukemia (MPAL), erythroid lineage is not defined, and to the best of our knowledge, only one other case with erythroid/B-cell biphenotypic acute leukemia has been reported previously. To establish the disease entity and clarify the pathophysiology of erythroid/lymphoid MPAL, additional cases need to be analyzed.


Assuntos
Leucemia Aguda Bifenotípica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Linfócitos B , Feminino , Glicoforinas , Humanos , Imunofenotipagem , Pessoa de Meia-Idade
15.
Cancer Genet ; 258-259: 7-9, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34225100

RESUMO

Biphenotypic acute leukemias (BAL) are known as a type of leukemia involving cells with myeloid and along with lymphoid origin, in which genomic changes are detected. It has been stated that the most common genomic changes in BAL are t(9;22) and the translocations of the 11q23 region, these anomalies cause poor prognostic effects. We detected trisomy 5 (+5) in addition to the double Ph chromosome in a case where we investigated the genomic changes using molecular and conventional cytogenetic methods. Bone marrow transplantation was planned due to the poor response to prednisone. According to the information we have obtained, our report will be the first article to discuss the aberrations found in addition to the Ph chromosome in BAL and the effect of these aberrations on prognosis. However, the double observation of the Ph chromosome, which has a poor prognostic effect, is expected to affect the prognosis more negatively, this case will contribute to the literature in terms of trisomy 5. We think that more case reports are needed to reveal the anomalies and their prognostic significance in BAL.


Assuntos
Aberrações Cromossômicas , Síndrome de Cri-du-Chat/genética , Rearranjo Gênico , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/patologia , Cromossomo Filadélfia , Trissomia/genética , Pré-Escolar , Cromossomos Humanos Par 5/genética , Humanos , Masculino , Prognóstico
16.
Br J Haematol ; 195(2): 289-292, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34254287
17.
Cancer Sci ; 112(6): 2287-2298, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33738896

RESUMO

Drug resistance is a significant obstacle to effective cancer treatment. Drug resistance develops from initially reversible drug-tolerant cancer cells, which offer therapeutic opportunities to impede cancer relapse. The mechanisms of resistance to proteasome inhibitor (PI) therapy have been investigated intensively, however the ways by which drug-tolerant cancer cells orchestrate their adaptive responses to drug challenges remain largely unknown. Here, we demonstrated that cyclin A1 suppression elicited the development of transient PI tolerance in mixed-lineage leukemia (MLL) cells. This adaptive process involved reversible downregulation of cyclin A1, which promoted PI resistance through cell-cycle arrest. PI-tolerant MLL cells acquired cyclin A1 dependency, regulated directly by MLL protein. Loss of cyclin A1 function resulted in the emergence of drug tolerance, which was associated with patient relapse and reduced survival. Combination treatment with PI and deubiquitinating enzyme (DUB) inhibitors overcame this drug resistance by restoring cyclin A1 expression through chromatin crosstalk between histone H2B monoubiquitination and MLL-mediated histone H3 lysine 4 methylation. These results reveal the importance of cyclin A1-engaged cell-cycle regulation in PI resistance in MLL cells, and suggest that cell-cycle re-entry by DUB inhibitors may represent a promising epigenetic therapeutic strategy to prevent acquired drug resistance.


Assuntos
Ciclina A1/metabolismo , Enzimas Desubiquitinantes/antagonistas & inibidores , Tolerância a Medicamentos , Leucemia Aguda Bifenotípica/tratamento farmacológico , Inibidores de Proteassoma/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Cromatina/metabolismo , Ciclina A1/genética , Resistencia a Medicamentos Antineoplásicos , Tolerância a Medicamentos/genética , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Leucemia Aguda Bifenotípica/genética , Leucemia Aguda Bifenotípica/metabolismo , Leucemia Aguda Bifenotípica/patologia , Metilação , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Prognóstico , Inibidores de Proteassoma/uso terapêutico , Ubiquitinação
19.
J Pediatr Hematol Oncol ; 43(3): e388-e394, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32925408

RESUMO

BACKGROUND: Ewing sarcoma breakpoint region 1 gene (EWSR1) rearrangements are largely associated with the Ewing sarcoma family of tumors. OBSERVATIONS: We report the first case of infantile, mixed phenotype acute leukemia, B/myeloid (bilineal and biphenotypic [B-lymphoid and B-lymphoid/myeloid]), with a t(2;22)(q35;q12). The EWSR1-fifth Ewing variant gene fusion and nonsense mutation in STAG2 were detected by next-generation sequencing and markedly high expression of fifth Ewing sarcoma variant mRNA detected by quantitative reverse transcription polymerase chain reaction. The patient was treated with a combined myeloid/lymphoid leukemia regimen followed by allogeneic stem cell transplant and was in complete remission at 3.8-year follow-up. CONCLUSIONS: Our case study underscores the importance of a comprehensive evaluation of acute leukemia and provides insights into the phenotype of EWSR1 rearranged neoplasms in the context of partner genes and cell type.


Assuntos
Proteínas de Ligação a DNA/genética , Leucemia Aguda Bifenotípica/genética , Leucemia Mieloide Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proteína EWS de Ligação a RNA/genética , Fatores de Transcrição/genética , Proteínas de Ciclo Celular/genética , Códon sem Sentido , Feminino , Humanos , Lactente , Translocação Genética
20.
Genes Chromosomes Cancer ; 60(2): 108-111, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33078871

RESUMO

Acute undifferentiated leukemia (AUL) is a very rare hematologic neoplasm that expresses no markers specific for either myeloid or lymphoid lineages. While commonly observed in several acute leukemias, KMT2A rearrangements in AUL have been rarely reported in the literature. We report the third case to our knowledge of AUL harboring a KMT2A rearrangement. Furthermore, the KMT2A/GIMAP8 gene fusion identified in this case represents a novel KMT2A rearrangement.


Assuntos
GTP Fosfo-Hidrolases/genética , Histona-Lisina N-Metiltransferase/genética , Leucemia Aguda Bifenotípica/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Criança , Humanos , Leucemia Aguda Bifenotípica/patologia , Masculino
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