V617F JAK2 Mutation and Bone Marrow Fibrosis Define Subgroups Of Patients With Polycythemia Vera and Essential Thrombocythemia With Shared Clinicobiological Profiles

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5268-5268
Author(s):  
Panagiotis Baliakas ◽  
Vassiliki Douka ◽  
Michalis Iskas ◽  
Tasoula Touloumenidou ◽  
Angeliki Paleta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Jak2 V617f ◽  
Age At Diagnosis ◽  
Advanced Age ◽  
Jak2 V617f Mutation ◽  
Hydroxyurea Treatment ◽  
V617f Mutation ◽  
Wbc Count

Abstract The JAK2 V617F mutation is of high diagnostic value in the evaluation of myeloproliferative neoplasms (MPN) as it helps to document clonality; in addition, it may also predict for response to hydroxyurea treatment. According to recent studies, the presence of bone marrow (BM) fibrosis at diagnosis may be associated with the clinical evolution of MPNs, in particular development of secondary acute myeloid leukemia (AML) or transformation to myelofibrosis (MF), however the underlying mechanisms remain unknown. In this study we characterized in detail subgroups of patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) carrying the JAK2 V617F mutation (M-JAK2) or displaying BM fibrosis at diagnosis with the ultimate aim of identifying potential associations and/or overlapping phenotypes. The present single-institution patient cohort included 118 cases diagnosed according to WHO 2008 criteria. Patient characteristics were as follows: (i) Diagnosis: PV/ET, 37/82; (ii) Gender: male/female, 58/60; (iii) median age at diagnosis: 59.8 years (range, 25-90). M-JAK2 was detected in 86/118 (72.9%) cases [PV: 32/37 (86.5%) - ΕΤ: 54/82 (65%)]. BM fibrosis was observed in 28/112 (25%) cases [PV: 10/34 (29.4%), ΕΤ: 18/78 (23%)], grade I in 24/28 (85%) cases and grade II in 4 cases (all with ΕΤ). Thirteen patients without BM fibrosis at diagnosis underwent a second BM biopsy at a median time of 4.7 years (range, 1-10): BM fibrosis was observed in 5/13 (38.4%), 4 carrying M-JAK2, of whom only one had received anagrelide before the second BM biopsy. With a median follow up of 6 years (range 1-10), one of these five patients developed AML. There was no statistically significant association between M-JAK2 and BM fibrosis at diagnosis, neither in the entire cohort, nor in each MPN (ET or PV) separately. In PV: (i) M-JAK2 was significantly (p<0.05) associated with advanced age at diagnosis, increased hemoglobin levels (Hb) and white blood cell (WBC) count at diagnosis; (ii) the presence of BM fibrosis demonstrated a strong trend for correlation with increased platelet counts at diagnosis (p=0.08). In ΕΤ: (i) M-JAK2 was significantly (p<0.05) associated with advanced age at diagnosis, splenomegaly, increased WBC count and Hb levels at diagnosis, and increased incidence of thrombotic events (12/54 versus 1/28); (ii) BM fibrosis was correlated with increased WBC and platelet count at diagnosis. Neither M-JAK2 nor BM fibrosis were correlated with increased incidence of hemorrhagic events, development of secondary AML or the presence of other concurrent malignancy. Furthermore, neither of these two parameters had any impact on overall survival, it has to be noted though that patients were not treated uniformly. In conclusion, the present analysis did not document a statistically significant correlation between M-JAK2 and BM fibrosis. Nonetheless, the clinicobiological similarities of patient subgroups defined by either of these parameters, as well as the increased incidence of BM fibrosis in sequential BM samples amongst M-JAK2 patients are suggestive of common pathogenetic mechanisms. Disclosures: No relevant conflicts of interest to declare.

JAK2 Mutation Status in Granulocytes, Platelets and Erythrocytes Differs Between Polycythemia Vera and Essential Thrombocythemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5228-5228
Author(s):  
Kohtaro Toyama ◽  
Norifumi Tsukamoto ◽  
Akio Saito ◽  
Hirotaka Nakahashi ◽  
Yoko Hashimoto ◽  
...  
Keyword(s):  
T Cells ◽  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Mononuclear Cells ◽  
Rna Extraction ◽  
Jak2 V617f ◽  
Janus Kinase ◽  
Jak2 V617f Mutation ◽  
Mutation Status ◽  
V617f Mutation

Abstract Background The gain-of-function point mutation in Janus kinase 2 exon 14 gene (JAK2-V617F) influences the diagnosis of bcr/abl-negative chronic myeloproliferative disorders (CMPDs). We previously reported that analyzing platelets is advantageous in detecting the JAK2-V617F mutation, particularly in essential thrombocythemia (ET), when compared to granulocytes. However, there have been few reports analyzing the JAK2-V617F mutation in erythroid lineage cells, and comparing the mutation status in all three lineages. Method Study protocols were approved by the Institutional Review Board of Gunma University Hospital, and written informed consent was obtained from all the patients. Heparinized peripheral blood was obtained from 113 patients with CMPDs (82 with ET, 25 with polycythemia vera (PV), and 6 with primary myelofibrosis (PMF). After centrifugation, platelets were collected from the upper plasma layer. Remaining blood was mixed with Hank’s Balanced Salt Solution and was subjected to Ficoll-Hypaque density gradient centrifugation. Granulocytes were obtained from the pellet. Mononuclear cells were resuspended in RPMI 1640 medium; 5 × 105 cells were plated in duplicate in 1 ml of methylcellulose medium and cultured in a humidified atmosphere of 5 % of carbon dioxide at 37°C for 14 days in the presence of erythropoietin to obtain erythroid colonies (BFU-E). T-cells were obtained from the remaining mononuclear cells using anti-CD3 immunoconjugated magnetic beads. After extraction of DNA from granulocytes, T-cells and BFU-E, and RNA extraction from granulocytes and platelets, PCR amplification and sequencing of exon 14 of the Jak2 gene was performed to confirm the presence of JAK2-V617F mutations. To confirm the mutation status of granulocytes, T-cells and BFU-E, allele-specific PCR (AS-PCR) was performed. Results For ET, 57 out of 82 patients (69.5%) had the JAK2-V617F mutation. In the 57 patients with the JAK2-V617F mutation, 38 (67%) had the mutation in all three lineages, 5 had the mutation in granulocytes and platelets, 2 had the mutation in platelets and BFU-E, 10 patients had the mutation only in platelets and 2 patients had the mutation only in BFU-E. In contrast, for PV, 22/25 patients (88%) had the JAK2-V617F mutation. Of note, in 22 patients having JAK2-V617F mutation, 20 (91%) were JAK2-V617F mutation-positive in all three lineages; the remaining two patients had the mutation in either platelets or BFU-E. The frequency of JAK2-V617F in all three lineages was significantly higher in PV than in ET (p &lt; 0.05). For PMF, 5 of 6 patients had the mutation in granulocytes, and 3 of these had it in all three lineages. Conclusion Among JAK2-V617F mutation-positive CMPDs, most PV patients had the JAK2-V617F mutation in all three lineages, thus suggesting that the JAK2-V617F mutation occurs in progenitor cell(s) common to granulocytes, platelets and erythrocytes. In contrast, only 67% of ET patients had the JAK2-V617F mutation in three lineages; in the remaining cases, not all of the three lineages have the mutation. This difference in lineages showing the JAK2-V617F mutation between the ET and PV may be related to the pathophysiological differences in ET and PV. Furthermore, the heterogeneous mutation status in ET may be related to its heterogeneous clinical manifestation.

Analysis of JAK2 V617F Mutation and Its Clinical Significance in Patients with Thrombocythemia and Other Myeloproliferative Neoplasms in Chinese

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4687-4687
Author(s):  
Yue Xu ◽  
Changxin Yin ◽  
Han He ◽  
Lingling Shu ◽  
Fuqun Wu ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Jak2 Mutation ◽  
Western Countries ◽  
Arms Pcr ◽  
V617f Mutation

Abstract Abstract 4687 JAK2 mutation is commonly found in Philadelphia-negative myeloproliferative neoplasms (MPNs). In Western countries, this mutation is found in approximately 96 percent of people with polycythemia vera, half of individuals with essential thrombocythemia or primary myelofibrosis. We used the method of amplification refractory mutation PCR (ARMS-PCR) to investigate MPN patients in China. We focused our study on patients with essential thrombocythemia (ET). ARMS-PCR was used to detect JAK2 V617F mutation in the bone barrow (BM) or peripheral blood of 37 MPN patients, which consisting of 7 ET, 5 polycythemia vera (PV), 5 chronic myeloid leukemia (CML), 5 chronic idiopathic myelofibrosis (CIMF), as well as 15 suspected MPNs. 17 cases of JAK2 V617F mutation (45.9%) were found in 37 patients, including 4 ET (57.1%), 4 PV (80.0%), 3 CIMF (60.0%), 6 suspected MPNs (40.0%). We did not find JAK2 V617F in the patients with CML. Our results indicated that the frequency of JAK2 V617F mutation in bcr/abl-negative MPNs in Chinese is similar to that in MPN patients in Western countries. At the same time, ARMS-PCR can distinguish the mutation is heterozygous or homozygous. Most patients were heterozygous for JAK2 but only a few were homozygous. In conclusion, our study showed that JAK2 V617F mutation frequency in Chinese MPN patients is similar to that in patients with this disorder in the West. It is the major molecular genetic abnormality in bcr-abl negative MPN and it can be used for diagnosis of MPN in China. Disclosures: No relevant conflicts of interest to declare.

Sequential Analysis By Next Generation Sequencing of 18 Genes in Polycythemia Vera and Essential Thrombocythemia Reveals a Association Between Mutational Status and Clinical Outcome after 3-Year Follow-up

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2808-2808
Author(s):  
Damien Luque Paz ◽  
Aurelie Chauveau ◽  
Caroline Buors ◽  
Jean-Christophe Ianotto ◽  
Francoise Boyer ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Jak2 V617f ◽  
Primary Myelofibrosis ◽  
Jak2 V617f Mutation ◽  
Poor Prognostic Factor ◽  
Disease Evolution ◽  
Allele Burden ◽  
V617f Mutation

Abstract Introduction Myeloproliferative neoplasms (MPN) are molecularly characterized by driver mutations of JAK2, MPL or CALR. Other somatic mutations may occur in epigenetic modifiers or oncogenes. Some of them have been shown to confer a poor prognosis in primary myelofibrosis, but their impact is less known in Polycythemia Vera (PV) and Essential Thrombocythemia (ET). In this study, we investigated the mutational profile using NGS technology in 50 JAK2 V617F positive cases of MPN (27 PV and 23 ET) collected at the time of diagnosis and after a 3 year follow-up (3y). Patients and Methods All patients were JAK2 V617F positive and already included in the prospective cohort JAKSUIVI. All exons of JAK2, MPL, LNK, CBL, NRAS, NF1, TET2, ASXL1, IDH1 and 2, DNMT3A, SUZ12, EZH2, SF3B1, SRSF2, TP53, IKZF1 and SETBP1 were covered by an AmpliseqTM custom design and sequenced on a PGM instrument (Life Technologies). CALR exon 9 mutations were screened using fragment analysis. Hotspots that mutated recurrently in MPN with no sequencing NGS coverage were screened by Sanger sequencing and HRM. A somatic validation was performed for some mutations using DNA derived from the nails. The increase of a mutation between diagnosis and follow-up has been defined as a relative increase of twenty percent of the allele burden. An aggravation of the disease at 3y was defined by the presence of at least one of the following criteria: leukocytosis &gt;12G/L or immature granulocytes &gt;2% or erythroblasts &gt;1%; anemia or thrombocytopenia not related to treatment toxicity; development or progressive splenomegaly; thrombocytosis on cytoreductive therapy; inadequate control of the patient's condition using the treatment (defined by at least one treatment change for reasons other than an adverse event). Results As expected, the JAK2 V617F mutation was found in all patients with the use of NGS. In addition, we found 27 other mutations in 10 genes out of the 18 genes studied by NGS (mean 0.54 mutations per patient). Overall, 29 of 50 patients had only the JAK2 V617F mutation and no other mutation in any of the genes analysed. No CALR mutation was detected. Nine mutations that were not previously described in myeloid malignancies were found. The genes involved in the epigenetic regulation were those most frequently mutated: TET2, ASXL1, IDH1, IDH2 and DNMT3A. In particular, TET2 mutations were the most frequent and occurred in 20% of cases. There was no difference in the number or in the presence of mutations between PV and ET. At 3y, 4 mutations appeared in 4 patients and 15 out of 50 patients (9 PV and 6 ET) were affected by an allele burden increase of at least one mutation. At 3y, 24/50 patients suffered an aggravation of the disease as defined by the primary outcome criterion (16 PV and 8 ET). The presence of a mutation (JAK2 V617Fomitted) at the time of the diagnosis was significantly associated with the aggravation of the disease (p=0.025). Retaining only mutations with an allele burden greater than 20%, the association with disease aggravation is more significant (p=0.011). Moreover, a mutation of ASXL1, IDH1/2 or SRSF2, which is a poor prognostic factor in primary myelofibrosis, was found in 8 patients, all having presented an aggravation of their disease (p=0.001). Only 4 patients had more than one somatic mutation other than JAK2 V617F and all of them also had an aggravation at 3y (p=0.046). In this cohort, appearance of a mutation at 3y was not associated with the course of the disease. Conversely, the increase of allele burden of at least one mutation was associated with an aggravation (p=0.019). Discussion and conclusion Despite the short follow-up and the limited number of patients, this study suggests that the presence of additional mutations at the time of the diagnosis in PV and TE is correlated to a poorer disease evolution. The increase of mutation allele burden, which reflects clonal evolution, also seems to be associated with the course of the disease. These results argue for a clinical interest in large mutation screening by NGS at the time of the diagnosis and during follow-up in ET and PV. Disclosures Ugo: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: ASH travel.

Analysis of JAK2 V167F Mutation in Myelodysplastic Syndromes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4591-4591 ◽  
Author(s):  
Elisa Fermo ◽  
Anna Zaninoni ◽  
Francesca G. Imperiali ◽  
Paola Bianchi ◽  
Mariangela Colombi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Myelodysplastic Syndromes ◽  
Prognostic Significance ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Myeloid Metaplasia ◽  
Mutational Status ◽  
V617f Mutation ◽  
Wbc Count

Abstract The somatic mutation JAK2 V617F has been identified as a pathogenic factor in typical chronic myeloproliferative diseases (MPD) such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis with myeloid metaplasia (MMF). In typical forms of myelodysplastic syndromes (MDS), JAK2 V617F mutation is rarely present (2–5%); on the contrary, it has been found with higher prevalence in patients with RARS-T (i.e. MDS/MPD-U with platelet count >600×109/L and ringed sideroblasts more than 15%) and in a subgroup of MDS patients with isolated 5q deletion and a proliferative bone marrow. In this study we analysed the JAK2 V617F mutational status in 53 MDS patients (26 males, 27 females; median age at the time of the study 76 years, range 45–91). Patients were classified as follows: 4 cases 5q- syndrome, 3 RCMD, 5 MDS/MPD, 1 MDS-U, 23 RA, 12 RARS, 5 RAEB. DNA was extracted from purified granulocytes; all samples were analyzed by allele-specific polymerase chain reaction (PCR), according to Baxter el al (2005). DNA samples were further subjected to direct sequencing for confirmatory testing. The JAK2 V617F mutation was present in 3 cases, with an overall frequency of 5%. With respect to MDS subtype, 1 patient had RA and 2 RARS. Among the 12 RARS patients, the two V617F postive displayed thrombocytosis (680×109/L and 649×109/L), whereas none of the 10 RARS V617F negative patients showed high platelet counts (median Plt 157×109/L, range 5–422×109/L). In one JAK2 mutant case, thrombocytosis required treatment with hydroxyurea. Moreover, the two V617F positive RARS patients displayed higher WBC count (6.2×109/L and 8.5×109/L) than the V617F negatives (median WBC 4.05×109/L); no difference was observed in Hb levels. The JAK2 positive RA patient had 10% of sideroblasts in bone marrow, normal platelet and WBC count and no proliferative characteristics; since the occurrence of the mutation may be an early event and preceed the classical manifestations of MDS/MPD, a longer follow-up is necessary to determine its possible prognostic significance. Considering the V617F negative MDS cases, only one patient, diagnosed as MDS/MPD, showed a platelet count >600×109/L. In conclusion, we confirmed recent reports showing that JAK2 V617F is present with low prevalence (about 5%) in MDS; in particular, the JAK2 mutation identifies a subset of MDS patients with and “overlap” syndrome, characterised by proliferative bone marrow morphology and frequent thrombocytosis and leucocytosis, who may benefit from JAK2 specifically targeted therapies.

Molecularly Confirmed Polycythemia Vera with Elevated Endogenous Serum Erythropoietin Level: Diagnostic Algorithms Revisited.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4964-4964
Author(s):  
Paul J. Thurmes ◽  
David P. Steensma
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Bone Marrow Biopsy ◽  
Arterial Oxygen Saturation ◽  
Jak2 V617f ◽  
The Body ◽  
Jak2 V617f Mutation ◽  
Arterial Oxygen ◽  
V617f Mutation ◽  
Dissociation Curves

Abstract Background: It is widely accepted that an elevated serum endogenous erythropoietin (EPO) level in a patient presenting with erythrocytosis and a genuinely increased red cell mass makes a diagnosis of polycythemia vera (PV) extremely unlikely (Mossuz et al Haematologica2004:1194; Tefferi and Gilliland Mayo Clin Proc2005:947.) However, in the absence of a definitive molecular marker for PV, there is often uncertainty, especially when PV-associated clinical features are present. Here we describe 4 patients presenting with Budd-Chiari syndrome (BCS) and erythrocytosis who had EPO levels well above the normal reference range (Levy et al Hepatology1985:858), yet all had the newly described JAK2 V617F point mutation in myeloid cells, confirming PV. Methods and Results: A 30-year-old man presented in March 2005 with ascites, mild splenomegaly, abnormal liver tests, and erythrocytosis (hemoglobin (Hb) 18.6 g/dL) with a normal platelet count (187 x 10(9)/L). BCS was diagnosed by Doppler ultrasonography, transjugular venogram, and liver biopsy. While bone marrow examination showed hypercellularity and megakaryocyte clustering consistent with chronic myeloproliferative disorder (CMPD), his EPO level was elevated to 32 U/L (normal 4–16 U/L), suggesting secondary erythrocytosis. Arterial oxygen saturation, Hb oxygen-dissociation curves (P50), molecular studies of the globin loci, Hb chromatography, and CT scans of the body were all normal. Granulocyte DNA demonstrated the JAK2 V617F mutation (heterozygous/mixed clonality), absent in buccal cells, confirming PV. Karyotype was normal and BCR/ABL was not present. The patient was treated with phlebotomy, warfarin, and hydroxyurea. One month later, his EPO level was markedly reduced at 13 U/L. We hypothesized that since hepatocytes express low levels of EPO, a remnant of fetal erythropoiesis, acute necrosis from BCS could lead to transient EPO surge even in the presence of chronic EPO suppression from PV. We then reviewed clinical data from all 33 patients at our institution since 1995 with BCS that was ultimately believed to be associated with PV. We identified 13 such patients in whom endogenous EPO levels were measured. Most had a low EPO level at the time of diagnosis (range of &lt;1.5 to 9 U/L), but 3 of these patients were found to have an elevated EPO level. DNA was extracted from archival samples from these 3 patients; JAK2 V617F mutation was detected in all 3. Clinical presentations were as follows: Patient 1: 21-year-old woman with BCS and pulmonary embolus, Hb 15.9 mg/dL, EPO 28 U/L. Bone marrow biopsy was consistent with PV. Subsequent EPO level was 19U/L in the setting of progressive liver failure. Patient 2: 48-year-old woman with known PV receiving intermittent phlebotomy presented with BCS, Hb 17.2 mg/dL, EPO 25 U/L. Marrow was consistent with CMPD. Patient 3: 33-year-old woman presented with BCS, Hb 18.8 mg/dL, EPO 53 U/L. Bone marrow biopsy showed early CMPD. Conclusion: Elevated EPO levels do not exclude the diagnosis of PV, especially in the presence of BCS with hepatic necrosis. These cases highlight the continuing challenges in accurate PV and CMPD diagnosis and emphasize the importance of complementing clinical assessment with molecular genetic testing, including JAK2 mutation analysis.

Role of serum erythropoietin, erythropoietin-independent erythroid colony formation, and bone marrow assessment in the diagnosis of polycythemia vera in patients with JAK2 V617F mutation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7085-7085
Author(s):  
J. M. MacKenzie-Feder ◽  
C. Eaves ◽  
K. Lambie ◽  
A. Abdi-Ali ◽  
K. M. Ramadan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Jak2 V617f ◽  
World Health ◽  
Jak2 V617f Mutation ◽  
Number Of Patients ◽  
V617f Mutation ◽  
Minor Criteria ◽  
Mutant Cells ◽  
Serum Erythropoietin

7085 Background: The discovery of the JAK2 V617F mutation in over 95% of polycythemia vera (PV) patients has led to the development of the new 2008 World Health Organization diagnostic criteria for PV. These specify a requirement for an elevated hemoglobin (Hb, males: >185 g/L, females: >165 g/L) and either evidence of JAK2-mutant cells plus any one of the following minor criteria: a below normal level of serum erythropoietin (Epo), detectable Epo-independent erythroid colony (EEC) formation in vitro, or panmyelosis in the bone marrow, or two of the latter in the absence of detectable JAK2-mutant cells. However, in patients with an elevated Hb and JAK2V617F positivity, there are few data to determine whether any of the 3 minor criteria actually add an independent contribution to the diagnosis of PV. Methods: We performed a retrospective chart review of 77 patients who had an elevated Hb and were positive for the JAK2 V617F mutation and who also had a test for at least one of the 3 minor criteria (serum Epo level: n = 53; EEC formation: n = 66; bone marrow examination: n = 16) to determine the frequency of cases who might lack one or more of these. Results: Although the number of patients with a complete set of data was limited, the results, nevertheless, were sufficient to show that all 3 minor criteria were highly represented and all 77 of the patients analyzed (100%) were positive for at least one of them; i.e., 47 of 53 tested (89%) had a reduced serum Epo level; 65 of 66 tested (98%) had EECs and 15 of 16 tested (94%) had evidence of bone marrow panmyelosis. Conclusions: Neither the Epo level, nor the presence of EECs nor evidence of bone marrow panmyelosis provided additional diagnostic specificity in a population of 77 patients with both JAK2 V617F-positive cells and an elevated Hb. Consideration should be given to limiting serum Epo, EEC, and bone marrow assessments to JAK2 mutant-negative patients. No significant financial relationships to disclose.

The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera

Blood ◽  
2006 ◽  
Vol 108 (6) ◽  
pp. 1865-1867 ◽  
Author(s):  
Eric Lippert ◽  
Marjorie Boissinot ◽  
Robert Kralovics ◽  
François Girodon ◽  
Irène Dobo ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Jak2 V617f ◽  
Allelic Frequency ◽  
Jak2 V617f Mutation ◽  
Mrna Levels ◽  
Expression Levels ◽  
Allele Specific ◽  
V617f Mutation

AbstractWe determined the allelic frequency of the JAK2-V617F mutation in DNA and assessed the expression levels of the mutant and wild-type JAK2 mRNA in granulocytes from 60 patients with essential thrombocythemia (ET) and 62 patients with polycythemia vera (PV) at the time of diagnosis. Using allele-specific quantitative polymerase chain reaction (qPCR), we detected JAK2-V617F in 75% of ET and 97% of PV at diagnosis. The total JAK2 mRNA levels were elevated in ET, PV, and secondary and idiopathic erythrocytosis, suggesting that hyperactive hematopoiesis alters JAK2 expression. The expression levels of JAK2-V617F mRNA were variable but strongly correlated with the allelic ratio of JAK2-V617F determined in DNA. Thus, differences in JAK2-V617F expression, markedly lower in ET than in PV, reflected different percentages of granulocytes carrying the mutation. Moreover, allelic ratios higher than 50% JAK2-V617F, indicating the presence of granulocytes homozygous for JAK2-V617F, were found in 70% of PV at diagnosis but never in ET.

Megakaryopoiesis and platelet function in polycythemia vera and essential thrombocythemia patients with JAK2 V617F mutation

2008 ◽  
Vol 88 (2) ◽  
pp. 181-188 ◽  
Author(s):  
Norimichi Hattori ◽  
Kunihiko Fukuchi ◽  
Hidetoshi Nakashima ◽  
Takashi Maeda ◽  
Daisuke Adachi ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Platelet Function ◽  
Essential Thrombocythemia ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
V617f Mutation

Evaluation Of The JAK2-V617F Gene Mutation In Egyptian Patients With Essential Thrombocythemia and Polycythemia Vera

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5254-5254
Author(s):  
Maha Ibrahim El Zaafarany ◽  
A. Hasan Abdel-Ghaffar ◽  
Tawfik R. Elkhodary ◽  
Dalia A. Salem ◽  
Eman A. Soliman ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Hematological Parameters ◽  
Mutation Screening ◽  
Jak2 V617f ◽  
Janus Kinase ◽  
Jak2 V617f Mutation ◽  
Egyptian Patients ◽  
V617f Mutation

Abstract An activating mutation of Janus kinase 2 (JAK2-V617F) was previously described in chronic myeloproliferative disorders (MPD). In previously published studies, the frequency of the JAK2-V617F mutation was determined to be 80–90 % for patients with polycythemia vera (PV) and 40–70 % for essential thrombocythemia (ET). In this study, we analyzed the relationship between the JAK2-V617F mutation and clinical-hematological parameters in Egyptian patients with MPD and compared these findings with published studies from other geographic regions and previous studies in EGYPT. A total of 56 patients were studied; of which, 32 were diagnosed with PV and 24 with ET. The mutation status of JAK2 was determined using allele-specific oligonucleotide (ASO) PCR assay. We found that 53% of the PV group and 79% of the ET group were positive for the JAK2-V617F mutation. When all patients were analyzed; patient age, levels of WBCs, levels of hemoglobin, levels of platelets and splenomegaly were significantly different in patients with the JAK2-V617F mutation (p < 0.05). The JAK2-V617F mutation is frequently detected in the Egyptian patients with MPD, and especially in patients with ET. Hence, it would be useful to include JAK2 mutation screening in the initial evaluation of patients suspected to have MPD especially ET. Disclosures: No relevant conflicts of interest to declare.

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