Concomitant detection of BCR-ABL translocation and JAK2 V617F mutation in five patients with myeloproliferative neoplasm at diagnosis

2012 ◽  
Vol 35 (1) ◽  
pp. e4-e5 ◽  
Author(s):  
M. Cappetta ◽  
V. Pérez ◽  
M. N. Zubillaga ◽  
V. Elizondo ◽  
G. Manrique ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
V617f Mutation

The Decrease of JAK2 V617F Allele Burden in Leukemia Transformation of An Elderly Patient with Myelofibrosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4990-4990
Author(s):  
Su-Jiang Zhang ◽  
Jianyong Li ◽  
Wei Xu
Keyword(s):  
Conflicts Of Interest ◽  
Molecular Genetic ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Leukemia Cells ◽  
Elderly Aml ◽  
Genetic Abnormalities ◽  
V617f Mutation

Abstract Abstract 4990 Recently there were two different model about clone genesis of acute myeloid leukemia (AML) transformed from pre-existing JAK2 V617F positive myeloproliferative neoplasm (MPN). One model showed the leukemia cells were come from JAK2 V617F negative clone, however, the other indicated that the leukemia cells were still developed from JAK2 V617F positive clone. Here, we report a elderly AML patient who was developed from pre-existing myelofibrosis (MF) with homozygous JAK2 V617F mutation. In leuekmic transformation phase, heterozygous JAK2 V617F mutation was identified, supported the idea that the leukemia cells may be come from JAK2 V617F negative clone. Moreover, no other cytogenetic and molecular genetic abnormalities were further found. After one course of CAG regimen, complete remission was achieved. Further follow-up is still in progress. Disclosures No relevant conflicts of interest to declare.

Homologous Recombination of Wild TYPE JAK2, A NOVEL EARLY STEP In the DEVELOPMENT of Myeloproliferative Neoplasm

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2805-2805
Author(s):  
Mathias Vilaine ◽  
Damla Olcaydu ◽  
Ashot Harutyunyan ◽  
Jonathan Bergeman ◽  
Tiab Mourad ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Snp Array ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Wild Type ◽  
Jak2 Mutation ◽  
Chromosome 9P ◽  
V617f Mutation ◽  
Array Analyses

Abstract Abstract 2805 Background: Adequate expression and function of Jak2 in hematopoietic progenitors is critical for normal myelopoiesis. The JAK2 46/1 (GGCC) haplotype, a congenital particularity, predisposes to myeloproliferative neoplasm (MPN) both independently and through mutation of the JAK2 gene. The JAK2 V617F mutation and acquired homozygous status for JAK2 V617F are frequent in MPN. JAK2 V617F homozygosity is currently explained acquisition of the JAK2 V617F mutation followed by mitotic homologous recombination (HR) of JAK2 occurred between wild-type and mutant alleles, leading to uniparental disomy (UPD) of chromosome 9p (9pUPD). Here we report the cases of 2 PV patients (Na1061 and Na1253) with acquired homozygous status for the JAK2 46/1 haplotype yet their granulocytes carried <20% JAK2 V617F. Aim: To determine whether HR of JAK2 can precede the V617F mutation in MPN. Methods: Granulocyte DNA and CD3+ lymphocyte DNA were examined in parallel with qPCR assays specific for the wild type and 46/1 haplotypes using rs12343867, a JAK2 intron 14 marker, as well as 4 other single nucleotide polymorphisms (SNP) on chromosome 9p. 9pUPD clonality and length were determined using SNP array studies. Results: For both patients, lymphocytes were heterozygous for the 46/1 haplotype, confirming that granulocyte 46/1 homozygosity was acquired. Direct sequencing of the JAK2 and GNE genes and SNP array analyses revealed homologous recombination of part of the JAK2 gene (exons 6–19, patient Na1061) and of the complete 46/1 JAK2 haplotype (patient Na1253). Furthermore, for both patients, full length sequencing of JAK2 cDNA revealed no additional mutation. In both cases, HR of wild-type JAK2 was associated with growth advantage and high expression of recombined JAK2. For both patients, further SNP array analyses revealed partial 9pUPD concerning <30% cells, which correlated with %JAK2 V617F and was consistent with 9pUPD having occurred after JAK2 V617F (Figure 1). The distortion of SNP allelic differences was higher at the telomeric end than in the centromeric region of chr. 9p. This indicated 2 distinct partial 9pUPDs for Na1061 and 1 partial 9pUPD for Na1253. Conclusion: Homologous recombination involving wild type JAK2 can precede JAK2 mutation and 9pUPD in MPN. Thus multiple paths and diverse alterations of the JAK2 gene can lead to MPN in individuals carrying the JAK2 GGCC haplotype. We propose a new model with JAK2 HR as early event, followed or not by JAK2 mutation, or/and JAK2 mutation(s) facilitating subsequent recombination resulting in 9pUPD and JAK2 V617F homozygosity. Disclosures: No relevant conflicts of interest to declare.

Isolation, Expansion and Characterization of BM-Mesenchimal Cells (MSCs) in Patients Affected By Chronic Myeloproliferative neoplasm (MPN)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5142-5142
Author(s):  
Patrizia Chiusolo ◽  
Francesca Annunziata ◽  
Elena Rossi ◽  
Silvia Betti ◽  
Silvia Bellesi ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasm ◽  
Gene Mutations ◽  
Jak2 V617f ◽  
Cell Types ◽  
Erythropoietin Receptor ◽  
Jak2 V617f Mutation ◽  
Hematopoietic Stem ◽  
V617f Mutation

Abstract Introduction MSCs constitute a pivotal cell type capable of shaping both the architecture of the microenvironment and modulating communication between the various cell types through effects on the extracellular matrix (ECM) and by secretion of various growth factors and cytokines. MSCs and hematopoietic stem cells are thought to share the same mesenchymal origin. Some data confirm that MSCs express a functional erythropoietin receptor and JAK2-transduction pathway, but their role in the development and evolution of MPN is still not well known so our aim was the isolation, expansion and characterization of MSCs in patients affected by MPN. Some data indicates that BM-MSCs of patients affected by MPN do not carry the JAK2-V617F mutation. We studied 20 patients affected by MPN with the following characteristics: M/F 12/8, median age 53years, 8 affected by PV, 8 by ET and 4 by PMF. 15 patients were positive for JAK2 V617F mutation, 1 pts for cMPL and 2 were CARL mutations carriers. Methods: MSC were isolated by bone marrow fraction by gradient separation on Lympholyte cell separation media and expanded in culture with a specific medium (MesenCult) in plastic-adherent cultures up to the second passage. DNA was extracted from MSC using QIAmp DNA Mini kit and the study of recurrent alterations (JAK2, MPL and CARL gene mutations was performed). Results: MCS were expanded in 14 on 21 patients. Flow citometry analysis confirmed the standard MSC phenotype (CD45 negative, CD73 positive, CD90 positive and CD105 positive). The molecular analysis of JAKV617F, cMPL and CARL mutations resulted negative in all analyzed samples both in patients carriers of mutations and in wild type ones. Conclusions: We conclude that common mutations markers of MPN neoplasm are absent in the mesenchymal compartment of bone marrows of patients affected by MPN and are restricted to the neoplastic clone. This research project was supported by a grant from Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.) Disclosures No relevant conflicts of interest to declare.

scholarly journals Megakaryocytic morphology in Janus kinase 2 V617F positive myeloproliferative neoplasm

2017 ◽  
Vol 06 (02) ◽  
pp. 075-078
Author(s):  
Shuchi Ghai ◽  
Sharada Rai
Keyword(s):  
Bone Marrow ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Janus Kinase ◽  
Jak2 V617f Mutation ◽  
Fisher Exact Test ◽  
Janus Kinase 2 ◽  
Bone Marrow Biopsies ◽  
V617f Mutation

Abstract Context: Alterations in megakaryocyte morphology are the hallmark of myeloproliferative neoplasms (MPNs). These neoplasm are also associated with Janus kinase 2 (JAK2) V617F mutation in nearly 95% patients with polycythemia vera (PV), 40% patients of essential thrombocythemia (ET) and 50% patients of myelofibrosis (MF). The utility of megakaryocyte morphology in these disorders in correlation with JAK2 V617F remains unresolved. Aims: The aim of the study was to assess the morphology of megakaryocytes in bone marrow aspirates (BMAs) and bone marrow biopsies of patients of BCR-ABL negative MPNs with JAK2 V617F mutation. Settings and Design: This study was a retrospective and prospective, hospital-based study undertaken for a period ranging from January 2011 to April 2015. Subjects and Methods: Assessment of morphological features of megakaryocytes in 15 BMAs and their respective biopsies which included seven cases of PV, three cases of ET, and five cases of MF with JAK2 V617F mutation. Statistical Analysis Used: Chi-square test and Fisher exact test were used to compare the different features of megakaryocytes. Software version SPSS 13.0 was used. Results: Megakaryocytes in ET were found to have characteristically large size with staghorn multinucleated nuclei and exhibiting large amount of cytoplasm. MF showed dense clustering of megakaryocytes with staghorn nucleus along with sinusoidal dilatation and intrasinusoidal hematopoiesis. PV showed loose and dense clustering of megakaryocytes with a predominance of cloud-like nuclei. Few of the megakaryocytic morphologic features showed overlap between MF and PV and between ET and early MF. Conclusions: Megakaryocytic morphology can aid in the accurate diagnosis of the different subcategories of MPNs. This would help in categorization of clinically suspicious patients of JAK2 V617F negative patients.

JAK2 (V617F) Mutation and Cerebral Venous Thrombosis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3339-3339
Author(s):  
Ida Martinelli ◽  
Serena Maria Passamonti ◽  
Eugenia Biguzzi ◽  
Franca Franchi ◽  
Francesca Gianniello ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thrombosis ◽  
Whole Blood ◽  
Cerebral Venous Thrombosis ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
V617f Mutation

Abstract Abstract 3339 Background. Whether or not cerebral venous thrombosis, such as splanchnic venous thrombosis, can be the first manifestation of an underlying myeloproliferative neoplasm is currently unclear. Methods. Patients with cerebral venous thrombosis were tested for the JAK2 (V617F) mutation within one year from the onset of thrombosis and were followed until the development of a myeloproliferative neoplasm or censored at the end of follow-up. Results. Ten of 152 patients (6.6%) carried the JAK2 (V617F) mutation. Three of them had known acquired risk factors for thrombosis and 5 had thrombophilia. The median duration of follow-up was 7.8 years (6 months to 21.3 years). Six patients met the diagnostic criteria for myeloproliferative neoplasm at the time of cerebral venous thrombosis, while three additional patients developed the disease during the follow-up, for an annual incidence of 0.26% patient-years (95% CI 0.05–0.64). The last patient has no evidence of disease after three years of follow-up. Patients without the JAK2 (V617F) mutation at the time of cerebral venous thrombosis were re-tested at the end of the follow-up and remained negative, with normal whole blood counts [log-rank test c2: 159 (p<0.0001)]. Hence, a myeloproliferative neoplasm was diagnosed in 90% of patients with the JAK2 (V617F) mutation and in none of those without (Fisher's exact test p<0.0001). Conclusions. Cerebral venous thrombosis can be the first symptom of a myeloproliferative neoplasm. Thus, patients with cerebral venous thrombosis should be tested for the JAK2 (V617F) mutation, irrespective of whole blood counts and the presence of other risk factors for thrombosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluation of High Resolution Melting Technique for Detection of JAK2-V617F Mutation in Formalin-Fixed Paraffin-Embedded Specimen from Myeloproliferative Neoplasm Cases

2020 ◽  
Vol 18 (2) ◽  
Author(s):  
Mohammad Reza Abdullahi ◽  
Nor Zamzila Abdullah ◽  
Rosmawati Ismail ◽  
Naznin Muhammad ◽  
Norlelawati A. Talib
Keyword(s):  
High Resolution ◽  
High Resolution Melting ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Polycythaemia Vera ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
V617f Mutation ◽  
Formalin Fixed

Myeloproliferative neoplasm (MPN) is a group of myeloid disorders which leads to erythrocytosis, thrombocytosis and leucocytosis. MPN with BCR-ABL positive is chronic myeloid leukaemia (CML) while BCR-ABL negative MPN includes polycythaemia Vera (PV), essential thrombocytemia (ET) and primary myelofibrosis (PMF). One of the major criteria for diagnosis of BCR-ABL negative MPN is the presence of JAK2-V617F mutation which is positive in 95% of PV and around 60% of ET and MF. Beside peripheral blood specimen, formalin-fixed paraffin-embedded (FFPE) marrow specimen can be used for detection of this mutation. Unfortunately, FFPE produces low quality DNA that put a challenge for successful amplification of DNA. We aimed to evaluate the utility of High Resolution Melting (HRM) analysis for detection of JAK2-V617F mutation in FFPE specimen from MPN cases. This study is a descriptive crosssectional study. Forty FFPE marrow specimens were retrieved from the years 2014-2016. Bio-Rad Precision Melt Analysis software was used for analysis of HRM data. Allele-specific PCR was done for validation of results. Positive samples were subjected to Sanger sequencing. JAK2-V617F mutation was positive in 13 out of 40 MPN cases. Level of agreement between HRM and AS-PCR was 97.5%. HRM is a rapid and powerful diagnostic assay which is suitable for detection of JAK2-V617F mutation in FFPE marrow specimen.

Germline JAK2 V617F mutation as a susceptibility gene causing myeloproliferative neoplasm in first-degree relatives

2020 ◽  
Vol 61 (13) ◽  
pp. 3251-3254
Author(s):  
Hee Sue Park ◽  
Bo Ra Son ◽  
Kyeong Seob Shin ◽  
Hee Kyung Kim ◽  
Yaewon Yang ◽  
...  
Keyword(s):  
Susceptibility Gene ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
First Degree Relatives ◽  
V617f Mutation
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