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1.
Cancer Med ; 13(1): e6890, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38164059

RESUMO

BACKGROUND AND OBJECTIVE: Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by ineffective hematopoiesis due to stem cell abnormalities. Monosomy 7q aberrations are a common cytogenetic abnormality in MDS. Specifically, an unbalanced translocation der(1;7)(q10;p10) [der(1;7)] has been identified in MDS patients, which is a monosomy 7q aberration variant like -7/del(7q). However, knowledge of der(1;7)'s features remains limited. Existing studies have compared the clinical and genetic characteristics of der(1;7) to those of -7/del(7q) but yielded inconsistent findings. Accordingly, we conducted meta-analyses comparing der(1;7) to -7/del(7q). METHODS: Publications were searched from the following databases up to January 10, 2023: Pubmed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov. Eligible studies were assessed for risks of bias. Relevant data were extracted from included studies and analyzed using random-effects models. Publication bias was evaluated and sensitivity analyses were performed. RESULTS: The comparative meta-analyses included 405 MDS patients with der(1;7) from nine studies. The analysis revealed that der(1;7) was associated with a greater male preponderance (86.1% vs. 68.3%, Odds Ratios (ORs) 2.007, p < 0.01) than -7/del(7q), lower platelets counts compared to del(7q), higher hemoglobin levels than -7, lower absolute neutrophil counts, and higher percentage of patients with non-excess blasts (66.9% vs. 41.3%, ORs 2.374, p = 0.01) in comparison with -7/del(7q). The der(1;7) existed more as a sole karyotype aberration (55.6% vs. 37.0%, ORs 2.902, p = 0.02), co-occurred more often with +8 (22.7% vs. 4.2%, ORs 5.714, p = 0.04) whereas less -5/del(5q) (1.5% vs. 41.3%, ORs 0.040, p < 0.01) and complex karyotype (7.3% vs. 54.8%, OR 0.085, p < 0.01). The der(1;7) was associated with higher frequencies of RUNX1 (40.8% vs. 12.3%, ORs 4.764, p < 0.01), ETNK1 (28.1% vs. 2.5%, ORs 42.106, p < 0.01) and EZH2 (24.8% vs. 6.9%, ORs 3.767, p = 0.02) mutations, but less TP53 mutation (2.4% vs. 45.3%, ORs 0.043, p < 0.01). Moreover, der(1;7) patients had longer time to progression (Hazard Ratios (HRs) 0.331, p = 0.02), better overall survival (OS) than -7 patients (HRs 0.557, p < 0.01), but similar OS with del(7q) patients (HRs 0.837, p = 0.37). CONCLUSION: The findings revealed distinct clinical, cytogenetic, and molecular characteristics distinguishing der(1;7) from -7/del(7q), indicating der(1;7) defines a unique subtype within MDS with monosomy 7q. These findings support classifying der(1;7) as a separate MDS entity in future.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 7 , Síndromes Mielodisplásicas , Síndromes Mielodisplásicas/genética , Humanos , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 1/genética , Masculino , Feminino , Translocação Genética , Pessoa de Meia-Idade
2.
Int J Gynaecol Obstet ; 165(3): 1072-1084, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38149341

RESUMO

OBJECTIVE: The purpose of this preliminary investigation into the pathogenesis of pre-eclampsia was to screen the differential proteins in the serum of pregnant women with normal pregnancy and early-onset pre-eclampsia using isobaric tags for relative and absolute quantitation (iTRAQ), so as to identify serum biomarkers for the early diagnosis of pre-eclampsia. METHODS: We examined the peripheral serum of 58 normal pregnant women and 42 pregnant women with early-onset pre-eclampsia using iTRAQ; the differentially expressed proteins were screened for bioinformatics analysis; and the expression of candidate proteins human leukocyte antigen-1 (HLA-1) and ß2-microglobulin (ß2M) in placental tissues was detected using western blot. RESULTS: We identified a total of 63 differential proteins in the serum of patients from the normal control group and the pre-eclampsia group, and this included 24 up-regulated proteins and 39 down-regulated proteins. The western blot results of placental tissue showed reduced HLA-1 expression (1.12 ± 0.23) in the placenta in the pre-eclampsia group as compared with the normal control group (1.34 ± 0.22). Consistent with the results observed in the serum, ß2M in the placenta in the pre-eclampsia group was significantly elevated (1.05 ± 0.47) in comparison with the normal group (0.75 ± 0.33) (P < 0.05). CONCLUSION: In this study, we found that iTRAQ technology was useful for identifying differentially expressed proteins in the peripheral serum of pregnant women with pre-eclampsia, and that HLA-1 and ß2M, which may be involved in the occurrence of pre-eclampsia, show promise as predictive markers of pre-eclampsia.


Assuntos
Biomarcadores , Antígenos HLA , Placenta , Pré-Eclâmpsia , Microglobulina beta-2 , Adulto , Feminino , Humanos , Gravidez , Microglobulina beta-2/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Proteômica/métodos , Antígenos HLA/sangue
3.
Hematology ; 29(1): 2293513, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38149662

RESUMO

OBJECTIVES: In patients with acute promyelocytic leukemia (APL), additional chromosomal abnormalities (ACAs) are prognostic indicators. However, the clinical features of ACAs were not systematically reported in Chinese patients. Therefore, we enrolled a large cohort of APLs to demonstrate the clinical characteristics and prognostic value of ACAs. METHODS: 268 patients with newly diagnosed APL with t(15;17)(q24;q21) were retrospectively enrolled, and their clinical characteristics and the predictive value of ACAs were assessed between patients with the presence and absence of ACAs. RESULTS: APL patients with and without ACAs did not differ significantly in their clinical features or treatment response and clinical outcomes like overall survival (OS) and disease-free survival (DFS). It appeared to be substantially associated with worse OS in APL patients with trisomy 8, which was the most common ACA, although DFS was unaffected. Interestingly, the presence of ACAs or trisomy 8 affected OS and DFS in the subgroup of patients aged ≥60 years; by contrast, ACAs had no effect on OS or DFS in any treatment subgroup (ATRA + ATO/RIF or ATRA + ATO/RIF + CH or ATRA + CH), except for the ATRA + ATO/RIF + CH treatment subgroup, where their impact on DFS was less favorable. CONCLUSIONS: Our results suggested that OS and DFS were unaffected by ACAs. Nonetheless, in the subgroup of patients older than 60, the existence of ACAs or trisomy 8 appeared to impact OS and DFS negatively. Individuals with t(15;17) alone had a higher DFS and were more susceptible to ATRA + ATO/RIF + CH than individuals with t(15;17) ACAs.


Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína , Estudos Retrospectivos , Prognóstico , Aberrações Cromossômicas , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
4.
Front Immunol ; 14: 1243773, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841238

RESUMO

Immune checkpoint inhibitors (ICIs) are increasingly being used in the treatment of advanced human malignancies. ICIs-related adverse events, including pancreatitis and diabetes, have been individually characterized in the literature. The co-occurrence of ICIs-related pancreatitis with diabetes is rare and easily overlooked, but it is often severe or fatal. We present a patient with renal tumor resection who was treated with injection of the PD-L1 inhibitor toripalimab and eventually developed acute pancreatitis and fulminant type 1 diabetes mellitus. In addition, we conducted a literature review of ICIs-related pancreatitis with diabetes. The case in our report presented with paroxysmal abdominal pain and loss of appetite. Intravenous fluids and insulin infusion improved the patient's pancreatitis and explosive hyperglycemia. This article suggests that ICIs can affect endocrine and exocrine functions of the pancreas, while providing information and new perspectives for the diagnosis and treatment of this challenging rare disease, helping inspire clinicians for the early identification and effective management of similar cases.


Assuntos
Diabetes Mellitus Tipo 1 , Doenças do Sistema Endócrino , Neoplasias , Pancreatite , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Pancreatite/induzido quimicamente , Pancreatite/diagnóstico , Doença Aguda , Neoplasias/tratamento farmacológico
5.
Mol Carcinog ; 62(10): 1546-1562, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37493101

RESUMO

Circular RNAs (circRNAs), a type of endogenous noncoding RNA (ncRNA), exert vital roles in leukemia progression and are promising prognostic factors. Here, we report a novel circRNA, circSLC25A13 (hsa_circ_0081188), which was increased in acute myeloid leukemia (AML) patients with poor overall survival (OS) comparing to patients with good prognosis. Knockdown of circSLC25A13 in AML cells inhibited proliferation and increased cell apoptosis in vitro and in vivo. Enhanced circSLC25A13 expression promoted the survival of AML cells. Mechanistically, circSLC25A13 played as a microRNA sponge of miR-616-3p, which inhibited the expression of adenylate cyclase 2 (ADCY2). Downregulation of miR-616-3p and overexpression of ADCY2 partially rescued circSLC25A13 deficient induced cell growth arrest. In summary, through competitive absorption of miR-616-3p and thereby upregulating ADCY2 expression, circSLC25A13 promoted AML progression. Moreover, circSLC25A13 may represent a potential novel biomarker for the prognosis of AML and offer a potential therapeutic target for AML treatment.


Assuntos
Leucemia Mieloide Aguda , MicroRNAs , Humanos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética
6.
Dalton Trans ; 52(21): 7271-7278, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37170648

RESUMO

White-light diodes (WLEDs) are widely used in high-brightness applications owing to their outstanding advantages. However, current methods for preparing commercial WLEDs significantly deteriorate their optical properties and limit their use in high-power applications. To address this, inorganic materials, such as phosphor-in-glass (PiG), have been recently investigated as practical alternatives. In this study, a series of high-efficiency white-emitting PiG samples were prepared by mixing silicate glass powders with different particle size distributions and different concentrations of Y3Al5O12:Ce3+ (YAG:Ce3+) phosphors. The microstructure, transmittance, and photoluminescence properties of PiG were investigated. When the glass powder with the particle size ranges of 75-150 and 30-48 µm were mixed, at a ratio of 94 : 6, a silicate glass with a thickness of 0.8 mm and a maximum transmittance of 75% in the visible range was obtained. Under excitation with a 450 nm blue-light laser diode, PiG produced white light with a total luminescence efficiency of 194.64 lm W-1 and a total luminous flux of 623.9 lm. These results demonstrate that the optical performance of PiG can be effectively adjusted by adjusting the particle size distribution of silicate glass powder and the mixing concentration of the YAG:Ce3+ phosphor, thereby providing a tuning pathway for smart white-light devices.

7.
Bioengineered ; 13(4): 8538-8547, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35331081

RESUMO

This study aimed to investigate the roles of the lysine (K)-specific demethylase 5C (KDM5C)-bone morphogenetic protein-7 (BMP-7) signaling pathway in the pathogenesis of severe preeclampsia (sPE). A total of 180 pregnant patients were enrolled in the study and classified into three groups: an early-onset sPE group (EOsPE) (n = 60), a late-onset sPE group (LOsPE) (n = 60), and a control group (normal pregnancy; n = 60). The messenger RNA (mRNA) and protein expression levels of bone morphogenetic protein receptor II (BMPRII), BMP-7, and KDM5C were detected in placenta samples from the two sPE groups, and their sites were evaluated using immunohistochemistry (IHC). The sPE groups showed an increased KDM5C mRNA expression, and the EOsPE group showed a decreased BMP-7 and BMPRII mRNA expression compared with the LOsPE group. However, contradictory results were discovered in terms of protein expression. Immunostaining of KDM5C, BMP-7, and BMPRII was observed in villous trophoblast and extravillous trophoblast cells. Compared with the control group, the staining intensity of KDM5C in the placental tissue trophoblast cell nucleus and vascular endothelial cells of the sPE groups was weaker, while that of BMP-7 and BMPRII was stronger, and the staining intensity was more subjective in the LOsPE group. Consistent findings were obtained by IHC and Western blot analysis. KDM5C nuclear-cytoplasmic translocation may regulate sPE through BMP-7 and its receptors. The KDM5C-BMP-7 signaling pathway may also lead to less invasion and increased apoptosis of the trophoblast cells, which is involved in the pathogenesis of sPE.


Assuntos
Proteína Morfogenética Óssea 7 , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Histona Desmetilases , Pré-Eclâmpsia , Proteína Morfogenética Óssea 7/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Células Endoteliais/metabolismo , Feminino , Histona Desmetilases/genética , Humanos , Incidência , Lisina , Placenta/metabolismo , Pré-Eclâmpsia/genética , Gravidez , RNA Mensageiro/genética
8.
Front Med ; 16(3): 416-428, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34792736

RESUMO

Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.


Assuntos
Acrilamidas , Plaquetas , Megacariócitos , Piperazinas , Pirimidinas , Acrilamidas/farmacologia , Animais , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Diferenciação Celular , Megacariócitos/citologia , Megacariócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Piperazinas/farmacologia , Pirimidinas/farmacologia
9.
Dalton Trans ; 50(43): 15688-15695, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34693945

RESUMO

Nowadays, there is enthusiastic effort to develop luminescent thermometers used for remote and high-sensitivity temperature readout over a wide sensing range. Herein, Pr3+ and Gd3+ co-doped ZrO2 nanocrystals are designed, prepared and investigated by XRD, Raman spectroscopy, XPS, TEM, EDS, DRS, PLE and PL spectroscopy. Upon 275 nm irradiation, the PL spectrum of ZrO2:Pr3+,Gd3+ is found to be composed of a narrow emission peak at 314 nm (Gd3+ 6P7/2-8S7/2), a broad defect-related emission band at 400 nm, and several emission peaks in the wavelength region of 585-700 nm (Pr3+ 1D2-3H4, 3P0-3H6, and 3P0-3F2), which exhibit different thermal responses owing to the effects of the various non-radiative relaxation processes and trap energy levels. Accordingly, the luminescence intensity ratio (LIR) between the Pr3+ 1D2-3H4 and Gd3+ 6P7/2-8S7/2 transitions demonstrates excellent relative sensing sensitivity values ((2.32 ± 0.01)% K-1-(8.32 ± 0.05)% K-1) and low temperature uncertainties (0.08 K-0.28 K) over a wide temperature sensing range of 303 K to 573 K, which are remarkably better than those of many other luminescence thermometers. What is discussed in the present study may be conducive to broadening the research region of RE3+ doped luminescence thermometric phosphors, especially for materials with rich 4f-4f transition lines and defect-related luminescence.

10.
Biomark Res ; 9(1): 53, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34229751

RESUMO

Myelodysplastic syndrome with myelofibrosis (MDS-MF) has been associated with an inferior prognosis compared with MDS without MF. However, MDS-MF is not listed independently as a subtype of MDS, and its clinical and genetic characteristics remain poorly understood. We retrospectively compared 53 patients with MDS-MF (44 MF grade 1/MF1; 9 MF grade 2-3/MF2 - 3) and 31 with de novo MDS without MF (MDS). The leukemic transformation risks of both MDS-MF2 - 3 and MDS-MF1 were increased compared with the MDS group. To identify the potential mechanisms responsible for the leukemic transformation of MDS-MF, we performed single-cell sequencing for one MDS-MF2 - 3 patient before and after leukemic transformation to explore the variations in gene expression levels. In addition to upgraded expression levels of acute myeloid leukemia-related genes during leukemic transformation, expression levels of some inflammation-related genes (such as S100s, RNASE3, and CYBB) were also increased, and inflammation-related pathways were up-regulated. These results suggest that inflammation-related genes and pathways may play an important role in the leukemic transformation of MDS-MF.

11.
Front Oncol ; 11: 706798, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307175

RESUMO

The NUP214-ABL1 fusion gene is a constitutively active tyrosine kinase that can be detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL) patients, and it can also be found in B-cell acute lymphoblastic leukaemia (B-ALL). However the NUP214-ABL1 fusion in acute myeloid leukemia (AML) has not yet been reported. Up to now, the sensitivity of NUP214-ABL1-positive patients to tyrosine kinase inhibitor (TKI) is still controversial. Here we report the first case of an AML patient carrying NUP214-ABL1 fusion gene. The conventional AML chemotherapy regimen for the patient was successful. Identification of additional AML patients with NUP214-ABL1 fusion gene will provide treatment experience and prognostic evaluation.

13.
Br J Haematol ; 193(6): 1096-1104, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33764511

RESUMO

Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B-cell ALL, reports of adult T-cell ALL (T-ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)-based MRD at the end of induction (EOI-MRD). The present retrospective study included 94 adult patients with T-ALL. MRD was detected by six- to eight-colour FCM. Patients who were EOI-MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P = 0·0020), and a lower relapse-free survival (RFS) (5·4% vs. 61·0%, P = 0·0005) and overall survival (OS) (32·7% vs. 69·7%, P < 0·0001) than those who were EOI-MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo-HSCT) at their first remission, EOI-MRD positivity was predictive of post-transplant relapse (2-year CIR: 68·2% vs. 4·0%, P = 0·0003). Multivariate analysis showed that EOI-MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P = 0·046], RFS (HR 2·125, P = 0·048) and OS (HR 2·987, P = 0·017). In conclusion, EOI-MRD based on FCM was an independent prognostic factor for relapse and survival in adult T-ALL. For patients who underwent HSCT, EOI-MRD could be used to identify patients with a high risk of relapse after allo-HSCT.


Assuntos
Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida
14.
Mol Cytogenet ; 14(1): 10, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573663

RESUMO

Mixed phenotype acute leukemia (MPAL) is an uncommon type of leukemia. It is one kind of malignant clonal diseases that expresses more than one genealogical specific antigen simultaneously. Most MPAL patients are associated with clonal chromosomal abnormalities and molecular genetic changes, such as t(9;22) (q34;q11) and KMT2A (MLL) rearrangement. These specific abnormalities usually have important guiding significance in MPAL diagnosis, targeted therapy and prognosis judgment. In this paper, we reported a case of MPAL, T/myeloid (M5) with an unfrequent combination of PML-RARα positivity and t(15;17). The treatment was successful with chemotherapy for both AML and ALL with daunorubicin, cytarabine (DA) and vincristine, prednisone (VP). We reported here this suggestive MPAL case of rare disease condition and effective treatment, in order to provide experience for the early diagnosis and treatment of similar patients.

15.
Am J Hematol ; 96(3): 312-319, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306218

RESUMO

The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. The CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T-cell precursor (ETP) ALL than in patients with non-ETP-ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2-year overall survival (OS) and event-free survival (EFS) rates than patients without CDKN2A deletion (2-year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T-ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem-cell transplantation.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Adolescente , Adulto , Idoso , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , China/epidemiologia , Terapia Combinada , Análise Mutacional de DNA , DNA de Neoplasias/genética , Feminino , Transplante de Células-Tronco Hematopoéticas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Resultado do Tratamento , Adulto Jovem
16.
Clinics (Sao Paulo) ; 75: e2011, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206758

RESUMO

OBJECTIVE: The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1+ ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era. METHODS: We retrospectively studied a series of adult patients receiving TKI-based therapy to evaluate the prognostic impact of the normal karyotype (NK) (n=22) in BCR-ABL1+ ALL by comparison with the isolated Ph+ karyotype (n=54). RESULTS: There were no statistically significant differences in clinical characteristics and complete remission rate between the two groups. Compared with the isolated Ph+ group, the NK/BCR-ABL1+ group had a higher relapse rate (55.0% versus 29.4%, p=0.044). Overall survival (OS) and disease-free survival (DFS) were significantly shorter in the NK/BCR-ABL1+ group than in the isolated Ph+ group [median OS: 24.5 versus 48.6 (months), p=0.013; median DFS: 11.0 (months) versus undefined, p=0.008]. The five-year OS and DFS for patients with NK/BCR-ABL1+ were 19.2% and 14.5%, respectively; those for patients with isolated Ph+ were 49.5% and 55.7%, respectively. Thirty-four (44.7%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in this study. Among the patients who received allo-HSCT, the median OS and DFS in the NK/BCR-ABL+ group (n=9) were 35.5 and 27.5 months, respectively, while those in the isolated Ph+ group (n=25) were undefined. There was a trend of significant statistical difference in the OS between the two subgroups (p=0.066), but no significant difference in the DFS. Multivariate analysis revealed that NK was independently associated with worse OS and DFS in BCR-ABL1+ ALL patients [Hazard ratio (HR) 2.256 (95% confidence interval (CI), 1.005-5.066), p=0.049; HR 2.711 (95% CI, 1.319-5.573), p=0.007]. CONCLUSION: Our results suggest that the sub-classification of an NK could be applied in the prognostic assessments of BCR-ABL1+ ALL. In addition, allo-HSCT should be actively performed to improve prognosis in these patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Proteínas de Fusão bcr-abl/genética , Humanos , Cariótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
17.
Front Oncol ; 10: 1423, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974153

RESUMO

Background: Adult T-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy and significantly linked to poor outcomes. Early T-cell precursor (ETP) leukemia is a unique subtype of T-ALL. The aim of this study is to compare the differences between ETP and non-ETP ALLs in China. Methods: We retrospectively analyzed the records of 122 adult T-ALL patients diagnosed and treated at our center between January 2014 and June 2019. All the patients enrolled were categorized into ETP and non-ETP ALL by immunophenotype, and further statistical analyses about clinical data and prognostic factors were performed. Results: Among the 122 cases, the male-to-female ratio was 2.8:1, and the median age is 29 (range, 16-82) years. Except for 10 patients with insufficient immunophenotyping results, 47.3% (53/112) are ETP and 52.7% (59/112) are non-ETP. Compared with non-ETP patients, ETP-ALL patients had lower white blood cell counts and lactate dehydrogenase levels, while they were older and had higher platelet counts and fibrinogen levels (all p < 0.05). Complete remission (CR) was achieved in 68.0% (83/122) of patients, 64.2 and 76.3% in ETP and non-ETP, respectively (p = 0.160). In total, 44.6% (37/83) of patients relapsed. Allogeneic stem cell transplantation (allo-SCT) was successfully performed in 36.1% (44/122) of patients, of which 79.5% (35/44) were in CR1. With a median follow-up of 9.1 (range, 0.5-70.3) months, the estimated 2-year overall survival (OS) and relapse-free survival (RFS) rates for the cohort were 38.0 ± 5.1 and 39.1 ± 6.3%, respectively. In the ETP group, the 2-year OS rate was 40.7 ± 8.2% and the RFS rate was 47.2 ± 10.7%, while in the non-ETP group, the 2-year OS rate was 37.9 ± 7.0% and the RFS rate was 39.2 ± 8.3% (both p > 0.05). In the landmark analysis of CR1 patients who had a survival of more than 6 months, the allo-SCT group had significantly better survival outcomes than the chemotherapy group, and the 2-year OS rates and RFS rates were 80.1 ± 7.3 vs. 28.4 ± 8.4% and 68.9 ± 8.8 vs. 12.8 ± 7.2%, respectively (both p < 0.0001). A multivariate analysis suggests that allo-SCT acts as an independent prognostic factor for both OS and RFS. Conclusions: Our results revealed that ETP accounted for a high proportion of T-ALL in Chinese. There are no CR rates and prognosis differences between ETP and non-ETP. Allo-SCT in CR1 can significantly improve patients' survival.

18.
Biosci Rep ; 40(2)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31894843

RESUMO

OBJECTIVE: Depression is a common complication in Type 2 diabetes mellitus (T2DM); however, it has long been underrecognized and undertreated. In the present study, we aimed to evaluate the clinical effects of Wuling capsule, a compound traditional Chinese herbal medicine, on T2DM complicated with depression. METHOD: 66 patients were enrolled and randomly divided into Wuling capsule treatment group and placebo group, and finally 64 cases finished the present study. The levels of FPG, 2hPG, HbAlc, TNF-α, IL-6, SOD, MDA, Cor, ACTH, HOMA-ß, HOMA-IR and ISI of patients were evaluated and compared. The HAMD scale for patients were recorded. RESULT: After 12-week treatment, the HAMD scale decreased in both groups, and was lower in Wuling capsule group. The level of FPG in Wuling capsule group was significantly lower than in placebo group; however, no obvious changes of 2hPG and HbA1c were found. The levels of IL-6 and TNF-α were significantly decreased in both groups, and more obviously in Wuling capsule group. The level of SOD was increased while the level of MDA was decreased significantly in both groups, and the changes were more obviously in Wuling capsule group. The levels of Cor and ACTH were significantly decreased in both groups; however, there was no statistically significance between the two groups. Besides, the comparisons of HOMA-ß, HOMA-IR and ISI between the two groups were not statistically significant. CONCLUSION: Our results suggested that Wuling capsule ameliorated the depression in patients with T2DM, and also improved the state of inflammation and oxidative stress state. These results also strongly indicated the ability of clinical transformation of Wuling capsule in patients with T2DM in the future.


Assuntos
Afeto/efeitos dos fármacos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/sangue , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Biomarcadores/sangue , China , Depressão/sangue , Depressão/etiologia , Depressão/psicologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Resultado do Tratamento
19.
Front Med ; 14(3): 327-334, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31784918

RESUMO

This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P = 0.025), higher ß2-microglobulin levels (P = 0.036), and higher lactate dehydrogenase levels (P = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, P = 0.002; median OS 16.8 vs. 45.9 months, P < 0.001) were strongly associated with short progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P < 0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P = 0.006) and OS (P = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Mieloma Múltiplo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores , Células da Medula Óssea/metabolismo , Bortezomib/administração & dosagem , China , Intervalo Livre de Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/análise , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Talidomida/administração & dosagem , Microglobulina beta-2/análise
20.
Clinics ; 75: e2011, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1133363

RESUMO

OBJECTIVE: The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1+ ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era. METHODS: We retrospectively studied a series of adult patients receiving TKI-based therapy to evaluate the prognostic impact of the normal karyotype (NK) (n=22) in BCR-ABL1+ ALL by comparison with the isolated Ph+ karyotype (n=54). RESULTS: There were no statistically significant differences in clinical characteristics and complete remission rate between the two groups. Compared with the isolated Ph+ group, the NK/BCR-ABL1+ group had a higher relapse rate (55.0% versus 29.4%, p=0.044). Overall survival (OS) and disease-free survival (DFS) were significantly shorter in the NK/BCR-ABL1+ group than in the isolated Ph+ group [median OS: 24.5 versus 48.6 (months), p=0.013; median DFS: 11.0 (months) versus undefined, p=0.008]. The five-year OS and DFS for patients with NK/BCR-ABL1+ were 19.2% and 14.5%, respectively; those for patients with isolated Ph+ were 49.5% and 55.7%, respectively. Thirty-four (44.7%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in this study. Among the patients who received allo-HSCT, the median OS and DFS in the NK/BCR-ABL+ group (n=9) were 35.5 and 27.5 months, respectively, while those in the isolated Ph+ group (n=25) were undefined. There was a trend of significant statistical difference in the OS between the two subgroups (p=0.066), but no significant difference in the DFS. Multivariate analysis revealed that NK was independently associated with worse OS and DFS in BCR-ABL1+ ALL patients [Hazard ratio (HR) 2.256 (95% confidence interval (CI), 1.005-5.066), p=0.049; HR 2.711 (95% CI, 1.319-5.573), p=0.007]. CONCLUSION: Our results suggest that the sub-classification of an NK could be applied in the prognostic assessments of BCR-ABL1+ ALL. In addition, allo-HSCT should be actively performed to improve prognosis in these patients.


Assuntos
Humanos , Adulto , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Proteínas de Fusão bcr-abl/genética , Inibidores de Proteínas Quinases/uso terapêutico , Cariótipo
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