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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1533-1539, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627436

RESUMO

OBJECTIVE: To investigate the relationship between JAK2 gene mutation and clinical indicators in patients with myeloproliferative neoplasms (MPN). METHODS: 122 MPN patients in the Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2017 to January 2020 were retrospectively analyzed. The relationship between JAK2 gene mutation and sex, age, peripheral blood cell count, splenomegaly, and thrombosis and bleeding events were analyzed. RESULTS: In 122 patients with MPN, the patients with polycythemia vera (PV) accounted for 36 (29.5%), the patients with essential thrombocythemia (ET) accounted for 56 (45.9%), the patients with myelofibrosis (MF) accounted for 30 (24.6%). The JAK2 gene mutation rate in MPN patients was 64.6% (79/122), and the JAK2 gene mutation rate in PV, ET and MF groups were 77.7% (28/36), 60.7% (34/56) and 56.7% (17/30), the JAK2 gene mutation rate of the patients in PV group was statistically significant as compared with those in the ET group (P<0.05). The hemoglobin (Hb) count of the patients in JAK2 gene mutation group was higher than those in wild-type group ï¼»(150.0±39.6)g/L vs (129.4±38.9)g/L, P<0.05ï¼½; the white blood cell (WBC) count of the patients in JAK2 gene mutation group was higher than those in the wild type group ï¼»(9.5±4.7)×109/L vs (8.4±46.9)×109/L, P<0.05ï¼½. As for the patients in PV group, the platelet count of the patients in JAK2 gene mutation group was higher than those in the wild type group ï¼»(370.2±113.1)×109/L vs (264.8±63.9)×109/L, P<0.05ï¼½. The incidence of splenomegaly in MPN patients was 35.2% (43/122), and the incidence of splenomegaly in MF patients was 63.3% (19/30), and the incidence of splenomegaly in the patients in JAK2 gene mutation group in MF group (82.4%, 12/17) was significantly higher than those in the wild-type group (38.5%, 5/13) (P<0.05). CONCLUSION: The mutation rate of JAK2 gene in MPN patients is higher, and the mutation rate of JAK2 gene in PV patients is higher than that in ET and MF patients; JAK2 gene mutations in MPN patients are related to hemogram index; the incidence of splenomegaly is the highest in MF patients, and splenomegaly is related to the occurrence of JAK2 gene mutations in MF patients.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Humanos , Janus Quinase 2/genética , Taxa de Mutação , Transtornos Mieloproliferativos/genética , Estudos Retrospectivos
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1540-1547, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627437

RESUMO

OBJECTIVE: To analyze the disease types, clinical manifestations, efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant myeloproliferative neoplasms (MPN), and provide a reference for the diagnosis, treatment and prognosis of MPN. METHODS: The clinical characteristics, diagnosis, therapeutic efficacy and outcome of JAK2 V617F and BCR-ABL double-mutant MPN were analyzed comprehensitively by combining a clinical case diagnosed and treated in our hospital with literature cases from CNKI and PubMed databases. RESULTS: A total of 38 related literatures were retrieved from the two databases by searching "JAK2 V617F" and "BCR-ABL" as key words from 1990 to 2019, and 59 cases were involved. Among all the 60 cases, 41 were males (68.3%) with a median age of 61 (32-77) years old, while 19 were females (31.7%) with a median age of 58 (21-82) years old. The BCR-ABL fusion gene and JAK2 V617F mutation were found simultaneously in 21 cases (35%), 19 cases (31.7%) with JAK2 V617F mutation were found during the treatment of Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Ph+CML was detectable in 20 cases (33.3%) during the treatment of JAK2 V617F mutation positive MPN. Polycythemia vera (PV) was the most common MPN coexisting with CML (30%), followed by essential thrombocythemia (ET) (26.7%) and primary myelofibrosis (PMF) (21.7%). In addition, there were 13 cases (21.7%) not classified in the literature. Among the 60 cases, 35 CML patients were clearly staged, including 31 in the chronic phase, 3 in the accelerated phase, and 1 in the blast crisis phase. As for the subtypes of BCR-ABL fusion gene, there were 30 cases with clear classification, including 28 cases of p210, 1 case of p190 and 1 case of p230. CONCLUSION: As cases of BCR-ABL and JAK2 V617F double-mutant MPN are reported, simultaneous detection of JAK2 V617F mutation and BCR-ABL fusion gene in MPN patients is necessary to avoid misdiagnosis and missed diagnosis.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Idoso , Idoso de 80 Anos ou mais , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética
3.
Blood Adv ; 5(17): 3373-3376, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477817

RESUMO

The molecular causes of myeloproliferative neoplasms (MPNs) have not yet been fully elucidated. Approximately 7% to 8% of the patients carry predisposing genetic germline variants that lead to driver mutations, which enhance JAK-STAT signaling. To identify additional predisposing genetic germline variants, we performed whole-exome sequencing in 5 families, each with parent-child or sibling pairs affected by MPNs and carrying the somatic JAK2 V617F mutation. In 4 families, we detected rare germline variants in known tumor predisposition genes of the DNA repair pathway, including the highly penetrant BRCA1 and BRCA2 genes. The identification of an underlying hereditary tumor predisposition is of major relevance for the individual patients as well as for their families in the context of therapeutic options and preventive care. Two patients with essential thrombocythemia or polycythemia vera experienced progression to acute myeloid leukemia, which may suggest a high risk of leukemic transformation in these familial MPNs. Our study demonstrates the relevance of genetic germline diagnostics in elucidating the causes of MPNs and suggests novel therapeutic options (eg, PARP inhibitors) in MPNs. Furthermore, we uncover a broader tumor spectrum upon the detection of a germline mutation in genes of the DNA repair pathway.


Assuntos
Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Proteína BRCA1/genética , Reparo do DNA/genética , Células Germinativas , Humanos , Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética
4.
Clin Lab ; 67(9)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34542973

RESUMO

BACKGROUND: Myeloproliferative neoplasms (MPN) are hematopoietic disorders characterized by abnormal proliferation of the myeloid lineage. Three classic subtypes are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These disorders are well known for their association with the JAK2 V617F mutation, in addition to mutations in MPL exon 10, and JAK2 exon 12. CALR mutations were detected in approximately 20% to 25% of patients with ET and PMF and not in patients with PV. Most CALR mutations were deletions and insertions in exon 9, which caused frameshift mutations. METHODS: This study included 60 Taiwanese patients with MPN. We identified CALR mutations in patients with MPN using the high-resolution melting (HRM) analysis. Additionally, the HRM analysis was compared with ipsogen CALR RGQ PCR. To confirm the results of HRM and ipsogen CALR RGQ PCR, sequencing analysis was also conducted all the samples. RESULTS: Up to 6.25% of CALR mutations were successfully detected in patients with MPN using HRM analysis. Eight out of 65 patients (12.3%) were positive for the presence of CALR mutation, including p.L367fs*46 and p.K385fs*47. The results proved 100% comparable to those obtained using ipsogen CALR RGQ PCR. CONCLUSIONS: The HRM analysis and ipsogen CALR RGQ PCR are feasible and reliable techniques for the detection of CALR mutation. Furthermore, HRM offers several benefits, for example, it is time-saving, inexpensive, and does not require many personnel.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Calreticulina/genética , Humanos , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Receptores de Trombopoetina/genética
5.
Hematology ; 26(1): 663-669, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34493151

RESUMO

OBJECTIVE: Infections in ruxolitinib-treated myeloproliferative neoplasm (MPN) patients were reported frequently. This work aimed to systematically estimate the risk of infection associated with ruxolitinib in MPN patients. METHODS: The PUBMED, CNKI, EMBASE, Cochrane and CBM databases were searched to identify all related studies. Odds ratio (OR) and 95% confidence interval (CI) were used to express the difference between groups. I2 was calculated to evaluate heterogeneity. Revman software was used to conduct the analysis. RESULTS: Eleven randomized control trials were included in this analysis. The risk of overall infections was not different at the early stage of ruxolitinib use (OR, 95%CI: 1.23, [0.91, 1.67]). In the extension phase, overall infection was significantly lower in patients receiving ruxolitinib (OR, 95%CI: 0.53, [0.36, 0.79]). Herpes zoster infection was at higher risk both at early stage and in the extension phase (OR, 95%CI: 7.39, [1.33, 41.07]), (OR, 95%CI: 5.23, [1.46, 18.79]), respectively. CONCLUSION: Our study suggested that ruxolitinib increased the risk of herpes zoster infection. However, current studies were not enough to estimate the effects of ruxolitinib on the risk of overall infection in patients with myeloproliferative neoplasm.


Assuntos
Herpes Zoster , Transtornos Mieloproliferativos , Pirazóis , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Herpes Zoster/induzido quimicamente , Herpes Zoster/epidemiologia , Humanos , Masculino , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/epidemiologia , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Hematology ; 26(1): 691-696, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34493159

RESUMO

Objective: The 8p11 myeloproliferative syndrome [EMS] is a rare myeloproliferative disorder which usually develops rapidly with chromosomal translocation of the fibroblast growth factor receptor 1 gene. The gene has 15 fusion partners, including the breakpoint cluster region (BCR) gene on chromosome 22. Of all the tests available, chromosome karyotype determination is the most important for the diagnosis of EMS. Here, we describe one case of a patient characterized by marked increase of white blood cells and thrombocytopenia and diagnosed as EMS with t(8;22)(p11;q11) by chromosome karyotype.Methods: 28-year-old man was referred to our hospital. He had a onemonth history of intermittent coughing and a small amount of expectoration after catching a cold. As an outpatient, his complete blood count showed: WBC was 130.04 × 109/L with 80.20% granulocytes.Hematologic investigations, bone marrow analysis and genomic DNA sequencing studies were performed.Results: Despite additional chromosomal abnormalities,the patient progressed rapidly with a B blast cell clone in one month. After diagnosis inthree months, the patient underwent the haplo-identical BMT of his brother, followed up for three years, and had a high rate of survival.Conclusions: Our report provides a definite conceptual framework for a better understanding of the characteristics of The 8p11 myeloproliferative syndrome [EMS].


Assuntos
Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 8/genética , Transplante de Células-Tronco Hematopoéticas , Transtornos Mieloproliferativos , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-bcr/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Translocação Genética , Adulto , Aloenxertos , Humanos , Masculino , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia , Síndrome
7.
Rinsho Ketsueki ; 62(8): 1029-1037, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497189

RESUMO

The development of gene analysis in cancer is remarkable, and understanding of molecular pathology has been elucidated. Somatic mutations, that is, genetic analysis in cancer cells, have contributed to the accurate diagnosis of tumors, prognostic prediction, and detection of therapeutic targets. In contrast, germline mutations have been identified as the cause of hereditary diseases. In the past, symptom diagnosis was the main focus for hereditary diseases. However, genetic information has greatly contributed to its definitive diagnosis. For hematopoietic malignancies, the 2016 revision of the World Health Organization classification newly proposed a section on myeloid neoplasms with germline predisposition. Genetic predispositions characterized by the development of lymphoid neoplasms and solid tumors have also been reported. Since 2016, new findings such as SAMD9/9L mutation have been discovered. This chapter outlines the typical genetic predisposition to myelodysplastic syndrome/leukemia.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética
8.
Rinsho Ketsueki ; 62(8): 1050-1059, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497191

RESUMO

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN), wherein JAK2 V617F mutation exists as a common driver mutation, and the JAK-STAT pathway is constitutively activated. The treatment goal for ET and PV is the prevention of thrombosis and bleeding. The treatment strategy for ET is careful observation or antiplatelet therapy with or without cytoreductive therapy based on the thrombotic risk. The treatment strategy for all PV patients is phlebotomy with a target hematocrit of <45% in addition to antiplatelet therapy. Moreover, for patients at a high risk of thrombosis, additional cytoreductive therapy is considered beneficial. In this session, we discuss important points for ET diagnosis, thrombotic risk stratification, and the details of treatment strategy and current practice with evidence from clinical trials in ET. Furthermore, current topics in the treatment of ET and PV will be introduced with a focus on clinical data about interferon-α, which is reported to induce not only hematologic response but also molecular and histopathologic response in MPN.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Trombose , Hemorragia , Humanos , Janus Quinase 2/genética , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Trombocitemia Essencial/terapia , Trombose/etiologia , Trombose/prevenção & controle
9.
Rinsho Ketsueki ; 62(8): 1060-1069, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497192

RESUMO

Myeloproliferative neoplasms (MPN) are caused by somatic mutations in hematopoietic stem/progenitor cells and result in excessive increase in the blood cell mass in the peripheral blood and/or fibrosis in the bone marrow. JAK2, CALR, and MPL mutations are well-known driver mutations of MPN and are widely applied as diagnostic markers of MPN. Moreover, several studies using massive parallel sequencing technologies have shown that mutations in ASXL1, EZH2, SRSF2, and IDH1/2 affect the prognosis of overt primary myelofibrosis and have further clarified that the mutation order may influence the MPN phenotype. More recently, our group identified that CREB3L1 mRNA was overexpressed in a platelet- and megakaryocyte-specific manner in driver mutation positive MPN and that the quantitation of this gene expression can be used as a diagnostic marker for MPN. In this educational lecture, we discuss the clinical impacts of the mutations frequently identified in MPN patients.


Assuntos
Transtornos Mieloproliferativos , Neoplasias , Calreticulina/genética , Humanos , Janus Quinase 2/genética , Japão , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética
10.
Am J Case Rep ; 22: e932956, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34433800

RESUMO

BACKGROUND Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), are associated with pulmonary hypertension (PH) and malignant lymphomas. Although the underlying mechanisms have not been completely clarified, it has been suggested that the Janus kinase 2 (JAK2) mutation, which is frequently identified in PV, can be involved in the development and/or progression of these distinct diseases in patients with MPNs. However, no reports have described the coexistence of PH and malignant lymphoma in patients with MPNs. CASE REPORT A 79-year-old man being treated for PV for 27 years and PH for 5 years was hospitalized due to severe dyspnea at rest. His soluble interleukin-2 receptor levels gradually increased and the chest computed tomography showed remarkable progression of the lung lesions and an enlargement of the mediastinal and axillary lymph nodes. A lymph node biopsy was performed and the patient was diagnosed with diffuse large B-cell lymphoma (DLBCL). Owing to his poor condition, chemotherapy was not initiated, and he died on the 89th day of hospitalization. The pathological autopsy revealed the destruction of alveolar structures with neoplastic space-occupying lesions of DLBCL. Multifactorial features of PH associated with MPNs, including the intimal thickening of pulmonary arteries accompanied by megakaryocytes and obstructed pulmonary arteries with organized thrombi in the lung tissue specimens, were observed. We found a JAK2 mutation based on a genetic analysis of the patient's bone marrow. CONCLUSIONS We present the rare case of a patient who had PV with a JAK2 mutation, which coexisted with PH and DLBCL, and he developed severe refractory respiratory failure.


Assuntos
Hipertensão Pulmonar , Linfoma Difuso de Grandes Células B , Transtornos Mieloproliferativos , Policitemia Vera , Idoso , Medula Óssea , Humanos , Hipertensão Pulmonar/etiologia , Linfoma Difuso de Grandes Células B/complicações , Masculino , Policitemia Vera/complicações , Policitemia Vera/genética
12.
Blood Adv ; 5(16): 3163-3173, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34424319

RESUMO

Outcomes in patients with high-risk and treatment-resistant myelofibrosis (MF) post-JAK inhibitor therapy remain poor, with no approved drug therapies beyond the JAK inhibitor class. In certain clinical situations, such as severe thrombocytopenia, administration of most JAK inhibitors are contraindicated. Thus, there is an unmet medical need for the development of novel agents for patients with MF. SMAC mimetics [or inhibitor of apoptosis (IAP) antagonists] induce apoptosis in cancer cells. Because these agents are hypothesized to have increased activity in a tumor necrosis factor-α cytokine-rich microenvironment, as is the case with MF, we conducted a single-center, investigator-initiated phase 2 clinical trial, with a monovalent SMAC mimetic LCL161 (oral, starting dose, 1500 mg per week) in patients with intermediate to high-risk MF. In an older group, 66% with ≥2 prior therapies and a median baseline platelet count of 52 × 103/µL and 28% with ASXL1 mutations, we observed a 30% objective response by Revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria. Notably, 6 responding patients achieved clinical improvement of anemia: 4, hemoglobin response; 2, transfusion independence. Median OS was 34 months (range, 2.2-60.1+). Reductions of cIAPs were observed in all responders. The most common toxicity was nausea/vomiting (N/V) in 64% (mostly grade 1/2); fatigue in 46%; and dizziness/vertigo in 30%. There were 4 grade 3/4 adverse events (2, syncope; 1, N/V; 1, skin eruption/pruritis). There were 2 deaths during the study period, both unrelated to the study drug. SMAC mimetics may represent an option for older patients with thrombocytopenia or for those in whom prior JAK inhibitors has failed. This trial was registered at www.clinicaltrials.gov as #NCT02098161.


Assuntos
Transtornos Mieloproliferativos , Mielofibrose Primária , Apoptose , Humanos , Mielofibrose Primária/tratamento farmacológico , Tiazóis
13.
Curr Opin Hematol ; 28(5): 347-355, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34342292

RESUMO

PURPOSE OF REVIEW: Clinical and experimental studies have uncovered relevant clinical implications of clonal hematopoiesis. However, the true magnitude of this process, clonal dynamics over time and mechanisms of progression into overt malignancy remain to be largely elucidated. In this article, the consequences of clonal hematopoiesis, its significance in the context of cytopenia, and its implications in the clinical management of patients with myeloid malignancies are reviewed and discussed. RECENT FINDINGS: Clonal hematopoiesis has been associated with higher risk of hematologic cancers, as well as of death from cardiovascular causes. Clonal hematopoiesis has been proven clinically relevant in the context of disorders characterized by peripheral blood cytopenia, including aplastic anemia, cytopenia of undetermined significance, as well as unexplained anemia of the elderly. SUMMARY: The available evidence has been proving the utility of somatic mutational analysis in patients with unexplained cytopenia, as well as in those receiving a diagnosis of myeloid neoplasm, enabling more accurate diagnosis, risk assessment, effective therapeutic strategies and residual disease monitoring. The access to a minimally invasive assessment is paving the way for screening programs of clonal hematopoiesis in individuals with absent or mild hematologic phenotype, as well as for therapeutic targeting of preleukemia cells.


Assuntos
Hematopoiese Clonal , Neoplasias Hematológicas/metabolismo , Transtornos Mieloproliferativos/metabolismo , Neoplasias Hematológicas/etiologia , Neoplasias Hematológicas/patologia , Humanos , Transtornos Mieloproliferativos/etiologia , Transtornos Mieloproliferativos/patologia , Fatores de Risco
14.
Biomater Sci ; 9(18): 6266-6281, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34369483

RESUMO

Induced pluripotent stem cells (iPSCs) provide an extraordinary tool for disease modeling owing to their potential to differentiate into the desired cell type. The differentiation of iPSCs is typically performed on 2-dimensional monolayers of stromal cell or animal tissue derived extracellular matrices. Recent advancements in disease modeling have utilized iPSCs in 3-dimensional (3D) cultures to study diseases such as muscular dystrophy, cardiomyopathy, and pulmonary fibrosis. However, these approaches are yet to be explored in modeling the hematological malignancies. Transient myeloproliferative disorder (TMD) is a preleukemic stage, which is induced in 10-20% of children with trisomy 21 possessing the pathognomonic mutation in the transcription factor GATA1. In this study, we established a synthetic 3D iPSC culture system for modeling TMD via hematopoietic differentiation of customized iPSCs. A chemically cross-linkable PEG hydrogel decorated with integrin binding peptide was found to be permissive of hematopoietic differentiation of iPSCs. It provided a cost-effective system for the generation of hematopoietic stem and progenitor cells (HSPCs) with higher yield of early HSPCs compared to traditional 2D culture on Matrigel coated dishes. Characterization of the HSPCs produced from the iPSC lines cultured in 3D showed that the erythroid population was reduced whereas the megakaryoid and myeloid populations were significantly increased in GATA1 mutant trisomic line compared to disomic or trisomic lines with wild-type GATA1, consistent with TMD characteristics. In conclusion, we have identified a cost-effective tunable 3D hydrogel system to model TMD.


Assuntos
Síndrome de Down , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Pluripotentes Induzidas , Transtornos Mieloproliferativos , Animais , Diferenciação Celular , Síndrome de Down/genética , Hidrogéis , Transtornos Mieloproliferativos/genética
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1236-1241, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362508

RESUMO

OBJECTIVE: To analyze the comprehensive laboratory test data of BCR-ABL1 fusion gene and JAK2 V617F mutation co-expressed in myeloproliferative neoplasm (MPN) patients, and investigate its relative clinical significance. METHODS: Data of 1 332 MPN patients were comprehensively analyzed, BCR-ABL1 (P190/P210/P230) fusion gene and JAK2 V617F mutation were detected by real time-polymerase chain reaction (RT-PCR) technique, the CALR, MPL, JAK2 12 and 13 exon mutations were detected by the First Generation Sequencing, the bone marrow cell morphology and pathological characteristics were evaluated by bone marrow smear and biopsy technique, the immune phenotypes of bone marrow cells were evaluated by flow cytometry, the chromosome karyotypes of bone marrow cells were analyzed by chromosome G banding technique. RESULTS: Four of the 1 332 patients were found to have the co-existence of BCR-ABL1 fusion gene and the JAK2 V617F mutation, with a 0.3% incidence and a median age of 70 years old, including 2 cases of polycythemia vera, 1 case of primary myelofibrosis, and 1 case of chronic myeloid leukemia-accelerated phase. The clues of double positive genes of such patients at the time of initial diagnose could not be cued only by age, physical signs and cell morphology, they should be analyzed by comprehensive test data. CONCLUSION: The co-existence of BCR-ABL1 fusion gene and JAK2 V617F mutation in the same case is a kind of disease with special clinical significance. The application of multiple detection methods can improve the detection of this disease, which is conducive to early detection, reasonable diagnosis and treatment by clinicians.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Idoso , Proteínas de Fusão bcr-abl/genética , Humanos , Janus Quinase 2/genética , Laboratórios , Mutação , Transtornos Mieloproliferativos/genética
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1242-1246, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362509

RESUMO

OBJECTIVE: To explore the expression level of ETV6-ABL fusion gene in different cell populations in patients with myeloproliferative neoplasm (MPN) and therapeutic effect of tyrosine kinase inhibitor (TKI). METHODS: A 42-year-old man who presented with fever, marked leukocytosis and chronic myelogenous leukemia (CML) like MPN was reported. ETV6-ABL fusion gene was detected by real-time PCR and confirmed by direct sequencing. ETV6-ABL mRNA expression in each cell population sorted from peripheral blood by flow cytometry was detected by real-time PCR. RESULTS: ETV6-ABL fusion gene was found out in bone marrow cells and confirmed as type A by direct sequencing. ETV6-ABL fusion gene transcript level in polymorphonuclear cells was nearly 3.6-fold relative to that in total cells, which was significantly higher than that in T cell, B cell and monocyte subsets. The complete blood count (CBC) returned to normal level after treatment with imatinib (400 mg) daily for three months. After TKI treatment for 6 months, the ratio of ETV6-ABL/ABL decreased from 174.1% to 1.9%. CONCLUSION: ETV6-ABL fusion gene positive MPN may have a CML clinical presentation and is sensitive to TKI. ETV6-ABL fusion gene is specifically expressed in polymorphonuclear cells.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Transtornos Mieloproliferativos , Adulto , Proteínas de Fusão bcr-abl/genética , Genes abl , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Transtornos Mieloproliferativos/genética
17.
Medicina (Kaunas) ; 57(8)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34441019

RESUMO

Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized collectively by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Although the natural history of these neoplasms can be measured sometimes in decades more than years, the cytogenetics analysis can offer useful information regarding the prognosis. Cytogenetics has a well-established prognostic role in acute leukemias and in myelodysplastic syndromes, where it drives the clinical decisions. NGS techniques can find adverse mutations with clear prognostic value and are currently included in the prognostic evaluation of MPNs in scores such as MIPSS, GIPSS, MIPSS-PV, and MIPSS-ET. We suggest that cytogenetics (considering its availability and relative cost) has a role regarding prognostic and therapeutic decisions.


Assuntos
Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , Neoplasias , Análise Citogenética , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Prognóstico
18.
Medicina (Kaunas) ; 57(8)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34441027

RESUMO

Background and objectives Budd-Chiari syndrome (BCS) refers to a complete thrombotic obstruction of the venous hepatic outflow tract due to various etiologies and constitutes a rare indication for ortothopic liver transplantation (LT). Few studies investigated long-term outcomes after LT for BCS. The aim of this study was to examine potential risk factors for late mortality and to evaluate long-term outcomes after LT for BCS. Materials and methods: 46 patients received an LT for BCS between 1989 and 2019 at the transplant center of the Charité-Universitätsmedizin Berlin. We analyzed potential effects of disease etiology, vascular events, rejection, and immunosuppression on long-term survival after transplantation using Kaplan-Meier curves and Cox logistic regression. Results: Of the 46 patients, 70% were female and 30% were male. Median age at the time of transplantation was 36 years. A total of 41 vascular events, including 26 thrombotic and 17 hemorrhagic incidents, occurred. The 1 year, the 5 year, the 10 year, and the 20 year survival rates were 87%, 83%, 76%, and 60%, respectively. By comparison, survival rates of the liver transplant cohort across all other indications at our center were slightly inferior with 85%, 75%, 65%, and 46%, respectively. In the study population, patients with myeloproliferative disorders showed worse outcomes compared to patients with other causes of BCS. Conclusion: Liver transplantation for BCS showed excellent results, even superior to those for other indications. Vascular events (i.e., thrombotic or hemorrhagic complications) did not have any prognostic value for overall mortality. Patients with myeloproliferative disorders seem to have a disadvantage in survival.


Assuntos
Síndrome de Budd-Chiari , Transplante de Fígado , Transtornos Mieloproliferativos , Trombose , Síndrome de Budd-Chiari/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Trombose/etiologia
19.
Korean J Intern Med ; 36(5): 1190-1203, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34289585

RESUMO

BACKGROUND/AIMS: Recent changes in the diagnostic criteria for myeloproliferative neoplasms (MPNs) and increasing patient numbers necessitate updating of the data on vascular events in patients with such disorders. METHODS: In this single-center study, thrombotic and hemorrhagic events were retrospectively analyzed in patients diagnosed with essential thrombocythemia (ET), polycythemia vera (PV) prefibrotic/early primary myelofibrosis (pre-PMF), or PMF, based on the 2016 World Health Organization diagnostic criteria. RESULTS: Of a total of 335 consecutive patients (139 ET, 42 pre-PMF, 124 PV, and 30 PMF patients; 192 males and 143 females) of median age 64 years (range, 15 to 91), 112 (33.4%) experienced a total of 126 thrombotic events before diagnosis, at the time of diagnosis, or during follow-up over a median of 4.6 years (range, 0.1 to 26.5). Cerebrovascular thrombosis (18.8%) was the most common initial event, followed by coronary heart disease (10.1%) and splanchnic (1.5%) and peripheral thrombosis (1.5%). Arterial thrombosis was more common than venous thrombosis (31.3% vs. 2.1%, respectively; p = 0.001). Thrombosis was most frequent in PV patients (39.5%), followed by patients with pre-PMF (38.1%), ET (30.9%), and PMF (13.3%). Of the 112 patients who experienced thromboses, 53 (47%) and 39 (33.9%) had thrombotic events before and at the time of MPN diagnosis, respectively. Twenty-seven patients (8.1%) experienced 29 hemorrhagic events, of which gastrointestinal bleeding (n = 20) was the most common. CONCLUSION: Most thrombotic events occurred before or at the time of diagnosis, and the prevalence of arterial thrombosis was markedly higher than that of venous thrombosis in patients with MPN.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Trombose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/epidemiologia , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiologia , Estudos Retrospectivos , Trombose/epidemiologia , Trombose/etiologia , Organização Mundial da Saúde
20.
Curr Opin Hematol ; 28(5): 364-371, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232140

RESUMO

PURPOSE OF REVIEW: Bone marrow fibrosis is the progressive replacement of blood-forming cells by reticulin fibres, caused by the acquisition of somatic mutations in hematopoietic stem cells. The molecular and cellular mechanisms that drive the progression of bone marrow fibrosis remain unknown, yet chronic inflammation appears to be a conserved feature in most patients suffering from myeloproliferative neoplasms. RECENT FINDINGS: Here, we review recent literature pertaining to the role of inflammation in driving bone marrow fibrosis, and its effect on the various hematopoietic and nonhematopoietic cell populations. SUMMARY: Recent evidence suggests that the pathogenesis of MPN is primarily driven by the hematopoietic stem and progenitor cells, together with their mutated progeny, which in turn results in chronic inflammation that disrupts the bone marrow niche and perpetuates a disease-permissive environment. Emerging data suggests that specifically targeting stromal inflammation in combination with JAK inhibition may be the way forward to better treat MPNs, and bone marrow fibrosis specifically.


Assuntos
Medula Óssea , Neoplasias Hematológicas , Células-Tronco Hematopoéticas , Mielofibrose Primária , Medula Óssea/metabolismo , Medula Óssea/patologia , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia
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