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Chinese Journal of Hematology ; (12): 276-283, 2023.
Article in Chinese | WPRIM | ID: wpr-984615


Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Male , Female , Humans , Adult , Middle Aged , Aged , Blast Crisis/drug therapy , Primary Myelofibrosis/genetics , Prognosis , Splenomegaly , Retrospective Studies , Myeloproliferative Disorders/genetics , Mutation , Leukemia, Myeloid, Acute , Janus Kinase 2/genetics
Rev. colomb. gastroenterol ; 37(2): 237-241, Jan.-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1394956


Abstract Vein thrombosis of unusual sites such as the splanchnic region continues to be not only a diagnostic but also a therapeutic challenge for the clinician due to its manifestation and associated pathologies. Latent JAK2 (Janus kinase 2) positive myeloproliferative neoplasm associated with sticky platelet syndrome is unusual. We present a clinical case of a 38-year-old female patient who presented with sudden onset abdominal pain of a possible vascular origin. Splanchnic thrombosis was diagnosed in latent myeloproliferative neoplasm by identifying the JAK2V617F mutation and sticky platelet syndrome via platelet aggregometry. Off-label anticoagulation with rivaroxaban 20 mg/day was administered. During her outpatient follow-up, she did not suffer any new thrombotic episodes.

Resumen La trombosis venosa de sitios inusuales como la esplácnica continúa siendo un reto no solo diagnóstico sino también terapéutico para el clínico debido a su forma de presentación y las patologías asociadas. La neoplasia mieloproliferativa latente JAK2 (cinasa de Janus 2) positiva asociada con síndrome de plaqueta pegajosa es inusual. Se presenta un caso clínico de una paciente de 38 años de edad que debutó con dolor abdominal de inicio súbito que sugirió un posible origen vascular. Se diagnosticó trombosis esplácnica en relación con neoplasia mieloproliferativa latente por la identificación de la mutación de la JAK2V617F y síndrome de plaqueta pegajosa mediante agregometría plaquetaria. Se administró de manera off-label anticoagulación con rivaroxabán 20 mg/día. Durante su seguimiento ambulatorio no ha presentado nuevos episodios trombóticos.

Humans , Female , Adult , Blood Platelet Disorders/diagnosis , Viscera/blood supply , Venous Thrombosis/diagnosis , Myeloproliferative Disorders/diagnosis , Syndrome , Blood Platelet Disorders/genetics , Venous Thrombosis/genetics , Janus Kinase 2/genetics
Frontiers of Medicine ; (4): 403-415, 2022.
Article in English | WPRIM | ID: wpr-939874


The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

Humans , Biomarkers , Hydroxyurea/therapeutic use , Interferon Regulatory Factors/genetics , Janus Kinase 2/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , Phenotype , Primary Myelofibrosis/genetics , Thrombocythemia, Essential/genetics
Article in Chinese | WPRIM | ID: wpr-939693


OBJECTIVE@#To explore the relationship between clinical features, peripheral blood cell count, coagulation function, gene mutation and hemorrhagic events and thrombotic events in essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis(PMF) patients.@*METHODS@#Clinical data of 78 patients with ET, PV, and PMF who were admitted to the Second Affiliated Hospital of Chongqing Medical University between September 2019 and August 2020 were retrospectively analyzed. Information about sex, age, gene mutation, peripheral blood cell count, coagulation function, and hemorrhagic and thrombotic events was included, and the influence of these data on the occurrence of hemorrhagic and thrombotic events was estimated.@*RESULTS@#Among the 78 patients with myeloproliferative neoplasms, there were 47 cases of ET, 15 cases of PV, and 16 cases of PMF.A total of 10 patients (12.82%) experienced hemorrhagic events and 27 (34.62%) experienced thrombotic events. Male,patients aged ≥ 60 years, and patients with a JAK2V617F mutation were more likely to experience thrombotic events (P<0.05). Patients with thrombotic events had higher platelet (PLT) counts and fibrinogen (FIB) levels than patients without hemorrhagic-thrombotic events (P<0.05).White blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB) level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and international normalized ratio (INR) showed no statistical difference between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05). There was also no significant difference in the above-mentioned indexes between patients with hemorrhagic events and patients without hemorrhagic-thrombotic events (P>0.05). Among JAK2V617F positive myeloproliferative neoplasm patients, male patients were more likely to have thrombotic events (P<0.05), and patients with thrombotic events had higher platelet counts than those without hemorrhagic-thrombotic events (P<0.05). There was no significant difference in age, white blood cell count, red blood cell count, hemoglobin level, PT, APTT, FIB, TT or INR between patients with thrombotic events and patients without hemorrhagic-thrombotic events (P>0.05).@*CONCLUSION@#Sex, age, JAK2V617F mutation and platelet count have a certain value for predicting thrombosis in patients with myeloproliferative neoplasms.

Humans , Male , Hemoglobins/genetics , Hemorrhage , Janus Kinase 2/genetics , Mutation , Myeloproliferative Disorders/genetics , Polycythemia Vera/genetics , Retrospective Studies , Thrombocythemia, Essential , Thrombosis
Chinese Journal of Hematology ; (12): 107-114, 2022.
Article in Chinese | WPRIM | ID: wpr-929541


Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young Adult , Bone Marrow/pathology , Exons , Janus Kinase 2/genetics , Mutation , Mutation, Missense , Polycythemia Vera/genetics
Journal of Experimental Hematology ; (6): 1540-1547, 2021.
Article in Chinese | WPRIM | ID: wpr-922292


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@*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.

Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Fusion Proteins, bcr-abl/genetics , Janus Kinase 2/genetics , Myeloproliferative Disorders/genetics , Polycythemia Vera , Thrombocythemia, Essential
Journal of Experimental Hematology ; (6): 1533-1539, 2021.
Article in Chinese | WPRIM | ID: wpr-922291


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 [(150.0±39.6)g/L vs (129.4±38.9)g/L, P<0.05]; the white blood cell (WBC) count of the patients in JAK2 gene mutation group was higher than those in the wild type group [(9.5±4.7)×10@*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.

Humans , Janus Kinase 2/genetics , Mutation Rate , Myeloproliferative Disorders/genetics , Polycythemia Vera , Retrospective Studies
Journal of Experimental Hematology ; (6): 1236-1241, 2021.
Article in Chinese | WPRIM | ID: wpr-888544


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.

Aged , Humans , Fusion Proteins, bcr-abl/genetics , Janus Kinase 2/genetics , Laboratories , Mutation , Myeloproliferative Disorders/genetics , Polycythemia Vera
Journal of Experimental Hematology ; (6): 1998-2003, 2020.
Article in Chinese | WPRIM | ID: wpr-880005


OBJECTIVE@#To evaluate the proformance of multiplex PCR and capillary electrophoresis(MPCE) in the detection of JAK2V617F and CALR mutation in myeloproliferative neoplasms(MPN).@*METHODS@#The specificity primers of JAK2617F gene mutation and the primers of CALR gene were designed at the same time. The JAK2V617F and CALR gene primers were labeled with Cy5 fluorescence, all the primers were mixed in one tube for multiplex PCR and the PCR prodcuts were analysised by capillary electrophoresis. Then detection limit and sensitivity of MPCE were evaluated, and compared with comercial diagnostic kit.@*RESULTS@#JAK2V617F and CALR gene mutations could be detect by MPCE in one PCR test. JAK2V617F mutation could be detected at 0.01 ng genomic DNA, double positive JAK2V617F and CLAR gene mutations could be detected at 0.1 ng genomic DNA, at least 0.1% JAK2V617F positive mutation could be detected. The consistency between MPCE and commercial diagnostic gene mutation kit was 100%.@*CONCLUSION@#It is developed that a new gene mutation detection method of JAK2 V617F and CLAR gene based on MPCE in our experiment and it can be used as a new reagent for molecular diagnosis of MPN patients.

Humans , Calreticulin/genetics , Electrophoresis, Capillary , Janus Kinase 2/genetics , Mutation , Myeloproliferative Disorders/genetics , Neoplasms , Patients , Polymerase Chain Reaction
Rev. Assoc. Med. Bras. (1992) ; 65(6): 772-774, June 2019.
Article in English | LILACS | ID: biblio-1041042


SUMMARY The essential thrombocythemia is one of the seven described forms of myeloproliferative neoplasms. It is characterized by megakaryocytic hyperplasia with consequent thrombocytosis maintained in the peripheral blood, favoring the occurrence of thrombo-hemorrhagic phenomena. We present the case of an 81-year-old woman with a history of ischemic stroke in the context of a sustained thrombocytosis, which led to a spinal study and a search for the V617F mutation in the JAK2 gene, which was positive. The patient started cytoreductive therapy with hydroxyurea with favorable current evolution.

Humans , Female , Aged , Stroke/etiology , Thrombocythemia, Essential/complications , Risk Factors , Stroke/genetics , Janus Kinase 2/genetics , Thrombocythemia, Essential/genetics , Mutation
Bol. Acad. Nac. Med. B.Aires ; 95(1-2): 89-96, ene.-dic. 2017. tab
Article in Spanish | LILACS | ID: biblio-996856


OBJETIVO: evaluar asociación entre características basales de Trombocitemia Esencial (TE) y eventos. Materiales-métodos: estudio observacional retrospectivo, datos capturados prospectivamente. Población: adultos con TE confirmada seguidos en CH del IIHEMA. Resultados: 67 pacientes evaluables. Md 68 años. Femenino 44, Masculino 23. Seguimiento Md 6 años. Score riesgo Alto 40, Intermedio 15, Bajo 12. Hematocrito Md 41%. Hemoglobina Md 13.4 g/dL. Leucocitos Md 9.7x109/L. Plaquetas Md 852x109/L. Esplenomegalia 12. Cariotipo normal 40, alterado 5. JAK2 V617F positivo 29/41. BCR/ABL1 negativo 45/45. FRV 40. Eventos: 67. Sangrado, 21 pacientes, presentó asociación con leucocitosis: Md 12.2x109/L en el grupo con sangrado y 8.8x109/L en el grupo sin evento (p=0.003). El 76% del grupo con sangrado y el 36,96% del grupo sin evento tenían leucocitos >10.0x109/L (p= 0.003). Trombocitosis Md 1.204x109/L en el grupo con sangrados y 814.5x109/L en el grupo sin evento (p=0.0098), no alcanzó significación estadística al comparar proporción de pacientes con recuento normal (p=0.46). Tromboembolia, 16 pacientes, se asoció con leucocitosis (Md 11.9x109/L en el grupo con tromboembolia y 9.2x109/L en el grupo sin evento (p=0.02). 75% del grupo con eventos y 41% del grupo sin eventos tenían leucocitos >10.0x109/L (p=0.018)) y con trombocitosis (Md 1.182x109/L en el grupo con tromboembolia y 809x109/L en el grupo sin evento (p=0.04), pero no alcanzó significación estadística al comparar proporción de pacientes con recuento normal (p=0.5)). CONCLUSIÓN: la asociación entre trombocitosis extrema/leucocitosis y sangrado coincidió con la literatura; leucocitosis se asoció a tromboembolia. El JAK2 V617F no mostró asociación: analizaremos prospectivamente aumentando la población para esclarecer asociación y posible rol de terapias dirigidas en esta entidad. (AU)

OBJETIVE: asses association basal characteristics of Essential Trombocitemia (ET) and events. MATERIALS-METHODS: retrospective observational study, data captured prospectively. Population: adults with confirmed ET treated in CH of IHEMA. RESULTS: 67 evaluable patients. Md 68-years-old. Female 44, Male 23. Follow up Md 6 years. Risk Score High 40, Intermeddle 15, Low 12. Hematocrit Md 41%. Hemoglobin Md 13.4 g/dL. Leukocytes Md 9.7x109/L. Platelets Md 852x109/L. Splenomegaly 12. Normal karyotype 40, abnormal 5. JAK2V617F positive 29/41. BCR-ABL1 negative 45/45. Vascular risk factors 40. EVENTS: 67. Bleeding, 21 patients, showed association with leukocytosis: Md 12.2x109/L in the group with bleeding and 8.8x109/L in the group without event (p=0.003). Leukocytes >10.0x109/L was seen in 76% of the group with bleeding versus 36.96% of the group without event (p= 0.003). Thrombocytosis Md 1.204x109/L in the group with bleeding and 814.5x109/L in the group without event (p=0.0098), but did not reach statistical significance when comparing with the proportion of patients with normal counts (p=0.46). Thromboembolism, 16 patients, showed association with both leukocytosis (Md 11.9x109/L in the group with thromboembolism and 9.2x109/L in the group without event (p=0.02). Leukocytosis >10.0x109/L was seen in 75% of the group with events and 41% of the group without event (p=0.018)) and with thrombocytosis (Md 1.182x109/L in the group with thromboembolism and 809x109/L in the group without event (p=0.04), but did not reach statistical significance when comparing with the proportion of patients with normal counts (p=0.5)). CONCLUSION: the association between extreme thrombocytosis/leukocytosis and bleeding was consistent with literature; leukocytosis was associated also with thromboembolism. JAK2 V617F mutated did not show association, we will prospectively analyze increasing the population to clarify its association and possible role of target therapies in this disease. (AU)

Humans , Male , Female , Adult , Middle Aged , Janus Kinase 2/genetics , Thrombocythemia, Essential/therapy , Prognosis , Retrospective Studies , Disease Management , Observational Studies as Topic
Rev. Assoc. Med. Bras. (1992) ; 62(7): 647-651, Oct. 2016. tab
Article in English | LILACS | ID: biblio-829517


Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications contribute to morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed. We present the application of this score and compare its results with the usual classification system. Method: We retrospectively evaluated the characteristics and risk factors for thrombosis of 46 patients with a diagnosis of ET seen in the last 6 years at Faculdade de Medicina do ABC (FMABC). Results: Thrombosis in the arterial territory was more prevalent than in venous sites. We observed that cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) were also risk factors for thrombosis (p<0.001). Age over 60 years and presence of JAK2 V617F mutation were not associated with the occurrence of thrombotic events. No patient classified by IPSET-thrombosis as low risk had a thrombotic event. Furthermore, using the IPSET-thrombosis scale, we identified two patients who had thrombotic events during follow-up and were otherwise classified in the low-risk group of the traditional classification. Leukocytosis at diagnosis was significantly associated with arterial thrombosis (p=0.02), while splenomegaly was associated with venous thrombotic events (p=0.01). Conclusion: Cardiovascular risk factors and leukocytosis were directly associated with arterial thrombosis. IPSET-thrombosis appears to be better than the traditional classification at identifying lower risk patients who do not need specific therapy.

Resumo Introdução: em pacientes com trombocitemia essencial (TE), complicações vasculares contribuem para morbidade e mortalidade. Para melhor predizer a ocorrência de eventos trombóticos, um escore prognóstico internacional de trombose para TE (IPSET-trombose) foi recentemente desenvolvido. Apresentamos aqui a aplicação desse escore e comparamos seus resultados com o sistema de classificação usual. Método: avaliamos retrospectivamente as características e os fatores de risco para trombose em 46 pacientes com diagnóstico de TE que foram atendidos nos últimos 6 anos na Faculdade de Medicina do ABC. Resultados: trombose em território arterial é mais prevalente que em sítio venoso. Observamos que fatores de risco cardiovascular (hipertensão, hipercolesterolemia, diabetes mellitus e tabagismo) foram considerados fatores de risco para trombose (p<0,001). Idade > 60 anos e presença de mutação JAK2 V617F não se associaram à ocorrência de eventos trombóticos. Nenhum paciente classificado como baixo risco pelo IPSET-trombose apresentou evento trombótico. Quando comparado à classificação de risco tradicional, IPSET-trombose foi capaz de identificar dois pacientes que evoluíram com trombose no seguimento e estavam categorizados no grupo de baixo risco. Leucocitose ao diagnóstico foi mais prevalente em pacientes que apresentaram trombose arterial (p=0,02), e esplenomegalia, entre aqueles com evento trombótico venoso (p=0,01). Conclusão: fatores de risco cardiovascular e leucocitose se associaram de forma direta com trombose arterial. IPSET-trombose parece ser melhor que a classificação tradicional na identificação de pacientes de baixo risco que não precisam de terapia específica.

Humans , Male , Female , Adolescent , Adult , Aged , Aged, 80 and over , Young Adult , Thrombosis/etiology , Risk Assessment/methods , Thrombocythemia, Essential/complications , Prognosis , Reference Values , Thrombosis/diagnosis , Brazil , Smoking/adverse effects , Retrospective Studies , Risk Factors , Diabetes Complications , Janus Kinase 2/genetics , Hospitals, Public/statistics & numerical data , Hypertension/complications , Middle Aged
Egyptian Journal of Medical Human Genetics [The]. 2016; 17 (2): 209-215
in English | IMEMR | ID: emr-180240


Background: Acute myeloid leukemia [AML] is a heterogeneous clonal disorder in terms of cytogenetic and molecular aberrations. Ten-Eleven-Translocation 2 [TET2], Kirsten rat sarcoma viral oncogene homolog [KRAS], and Casitas B-cell lymphoma [CBL] have an important role pathogenesis of acute myeloid leukemia [AML] and their activated mutations confer proliferative and survival signals

Aim: In this study, we aimed to find possible genetic markers for molecular analysis in childhood AML by screening hot-spot exons of TET2, KRAS, and CBL using Next Generation Sequencing [NGS] analysis. In addition, association between found variants and mutations of Januse Kinase-2 [JAK2] and Fms-Related Tyrosine Kinase [FLT3] were analyzed which are important prognostic risk factors for AML

Methods: Eight patients who were diagnosed with pediatric AML at Losante Pediatric Hematology- Oncology Hospital were included to the study. Hot-spot exons of TET2, KRAS and CBL genes were screened using the NGS method. Furthermore, FLT3-Internal Tandem Duplicate [FLT3-ITD] and JAK2-V617F were analyzed by Real Time Polymerase chain Reaction [Real Time-PCR]

Results: In total, we identified 20 variants in studied genes by NGS. In our patient group, 16 variants in the TET2 [seven novel, seven missense and two silent], two variants in the KRAS [one missense and one intronic] and two variants in the CBL [two novel] were found. All of AML patients were found negative for JAK V617 F. Three of the eight patients [37.5%] showed mutations of both FLT3-ITD and TET2, KRAS, CBL

Conclusion: We found novel mutations forTET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations

Child , Child, Preschool , Female , Humans , Male , DNA-Binding Proteins/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins c-cbl/genetics , fms-Like Tyrosine Kinase 3/genetics , Janus Kinase 2/genetics , Sequence Analysis, DNA/trends
Article in English | WPRIM | ID: wpr-210698


Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.

Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Calreticulin/genetics , Disease-Free Survival , Gene Frequency , Genetic Association Studies , Janus Kinase 2/genetics , Mutation/genetics , Primary Myelofibrosis/genetics , Receptors, Thrombopoietin/genetics , Republic of Korea , Thrombocythemia, Essential/genetics
Article in English | WPRIM | ID: wpr-34580


BACKGROUND: Calreticulin (CALR) mutations were recently discovered in patients with myeloproliferative neoplasms (MPNs). We studied the frequency and type of CALR mutations and their hematological characteristics. METHODS: A total of 168 MPN patients (36 polycythemia vera [PV], 114 essential thrombocythemia [ET], and 18 primary myelofibrosis [PMF] cases) were included in the study. CALR mutation was analyzed by the direct sequencing method. RESULTS: CALR mutations were detected in 21.9% of ET and 16.7% of PMF patients, which accounted for 58.5% and 33.3% of ET and PMF patients without Janus kinase 2 (JAK2) or myeloproliferative leukemia virus oncogenes (MPL) mutations, respectively. A total of five types of mutation were detected, among which, L367fs*46 (53.6%) and K385fs*47 (35.7%) were found to be the most common. ET patients with CALR mutation had lower leukocyte counts and ages compared with JAK2-mutated ET patients. CONCLUSION: Genotyping for CALR could be a useful diagnostic tool for JAK2-or MPL-negative ET or PMF patients. CALR mutation may be a distinct disease group, with different hematological characteristics than that of JAK2-positive patients.

Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Amino Acid Sequence , Base Sequence , Calreticulin/genetics , DNA Mutational Analysis , Exons , Janus Kinase 2/genetics , Leukocyte Count , Molecular Sequence Data , Mutation , Myeloproliferative Disorders/diagnosis , Receptors, Thrombopoietin/genetics
Article in English | WPRIM | ID: wpr-29325


We evaluated the incidence, clinical characteristics, and prognostic impact of calreticulin (CALR) mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. In all, 48 ET and 14 PMF patients were enrolled, and the presence of CALR mutations was analyzed by direct sequencing. Patients were classified into three subgroups according to Janus kinase 2 (JAK2) V617F and CALR mutation status, and their clinical features and prognosis were compared. CALR mutations were detected in 15 (24.2%) patients, and the incidence increased to 50.0% in 30 JAK2 V617F mutation-negative cases. These included 11 patients with three known mutations (c.1092_1143del [seven cases], c.1154_1155insTTGTC [three cases], and c.1102_1135del [one case]) and 4 patients with novel mutations. ET patients carrying CALR mutation were younger, had lower white blood cell counts, and experienced less thrombosis during follow-up than those carrying JAK2 V617F mutation, while both patient groups showed similar clinical features and prognosis. In ET patients without JAK2 V617F mutation, CALR mutation did not significantly affect clinical manifestation and prognosis. In conclusion, CALR mutation analysis could be a useful diagnostic tool for ET and PMF in 50% of the cases without JAK2 V617F mutations. The prognostic impact of CALR mutations needs further investigation.

Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Calreticulin/genetics , DNA Mutational Analysis , Exons , Genotype , INDEL Mutation , Janus Kinase 2/genetics , Primary Myelofibrosis/diagnosis , Prognosis , Republic of Korea , Tertiary Care Centers , Thrombocythemia, Essential/diagnosis