Analysis of the exon 12 and 14 mutations of the JAK2 gene in Philadelphia chromosome-positive leukemia

Inami, Mitsuharu; Yamaguchi, Hiroki; Hasegawa, S.; Mitamura, Yoshio; Kosaka, Fumiko; Kobayashi, Ayako; Kimura, Shunsuke; Dan, Kazuo; Inokuchi, Koiti

doi:10.1038/sj.leu.2404953

Cited by 8 publications

(4 citation statements)

References 7 publications

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“… 27 , 28 , 29 , 30 JAK2 V617F is by far the most prevalent mutation in BCR-ABL1 -negative MPN (occurs in ∼95% of patients with PV, in ∼55% with ET and in ∼65% with PMF), 45 but it is also seen in some patients with myelodysplastic syndrome (MDS)/MPN (for example, refractory anemia with ring sideroblasts and thrombocytosis) 46 , 47 , 48 and, rarely, in primary acute myeloid leukemia (AML), MDS or CML. 49 , 50 , 51 , 52 However, this should not undermine its broad specificity to patients with myeloid neoplasms (including those with occult disease and splanchnic vein thrombosis) 53 , 54 and the fact that the mutation is not seen in patients with lymphoid neoplasms, reactive myeloproliferation or in healthy volunteers. 55 , 56 , 57 , 58 …”

Section: Jak2 Mutationsmentioning

confidence: 99%

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1

2010

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Myeloproliferative neoplasms (MPNs) originate from genetically transformed hematopoietic stem cells that retain the capacity for multilineage differentiation and effective myelopoiesis. Beginning in early 2005, a number of novel mutations involving Janus kinase 2 (JAK2), Myeloproliferative Leukemia Virus (MPL), TET oncogene family member 2 (TET2), Additional Sex Combs-Like 1 (ASXL1), Casitas B-lineage lymphoma proto-oncogene (CBL), Isocitrate dehydrogenase (IDH) and IKAROS family zinc finger 1 (IKZF1) have been described in BCR-ABL1-negative MPNs. However, none of these mutations were MPN specific, displayed mutual exclusivity or could be traced back to a common ancestral clone. JAK2 and MPL mutations appear to exert a phenotype-modifying effect and are distinctly associated with polycythemia vera, essential thrombocythemia and primary myelofibrosis; the corresponding mutational frequencies are ∼99, 55 and 65% for JAK2 and 0, 3 and 10% for MPL mutations. The incidence of TET2, ASXL1, CBL, IDH or IKZF1 mutations in these disorders ranges from 0 to 17% these latter mutations are more common in chronic (TET2, ASXL1, CBL) or juvenile (CBL) myelomonocytic leukemias, mastocytosis (TET2), myelodysplastic syndromes (TET2, ASXL1) and secondary acute myeloid leukemia, including blast-phase MPN (IDH, ASXL1, IKZF1). The functional consequences of MPN-associated mutations include unregulated JAK-STAT (Janus kinase/signal transducer and activator of transcription) signaling, epigenetic modulation of transcription and abnormal accumulation of oncoproteins. However, it is not clear as to whether and how these abnormalities contribute to disease initiation, clonal evolution or blastic transformation.

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Section: Jak2 Mutationsmentioning

confidence: 99%

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1

2010

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“…The JAK2V617F mutation can occasionally be detected in patients with hematologic disorders other than the MPNs; given the similarities between this and the JAK2 exon 12 variants, it is therefore reasonable to question whether the latter may also occur in these disorders. JAK2 exon 12 mutations were found to be absent from patients with Ph‐positive acute lymphocytic leukemia (ALL) or CML and from patients with primary mediastinal large B‐cell lymphoma or de novo acute myeloid leukemia (AML) [65–67]. In contrast, JAK2 exon 12 mutations can occur in patients with refractory anemia with ringed sideroblasts and thrombocytosis (RARS‐T), defined as an nDS/MPN overlap syndrome, since it exhibits features of both ET and the myelodysplastic syndrome, RARS [62].…”

Section: Jak2 Exon 12 Mutations In Other Hematologic Disordersmentioning

confidence: 99%

The JAK2 exon 12 mutations: A comprehensive review

2011

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A variety of acquired mutations targeting JAK2 exon 12 are present in those patients with the myeloproliferative neoplasm, polycythemia vera, that lack the more common JAK2V617F mutation. Both mutation types perturb erythropoiesis, with individuals presenting with a raised hematocrit, reduced serum erythropoietin levels, and erythropoietin-independent erythroid progenitor cells. However, there are also phenotypic differences that, until recently, precluded a significant proportion of patients with a JAK2 exon 12 mutation from receiving an appropriate diagnosis. Here, we review the literature published on the JAK2 exon 12 mutations and compare the biology associated with these mutations with that of JAK2V617F. Am. J. Hematol. 86:668-676, 2011. V

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“…1 Conversely, no JAK2 mutation has been found in Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML). 2 Nevertheless, some rare cases of patients harboring both a BCR-ABL rearrangement and a JAK2V617F mutation have been reported in the literature, their coexistence appearing during the evolution of the disease. [3][4][5] Recently, Bornhäuser et al 6 described concurrent JAK2V617F mutation and BCR-ABL translocation in one case of myelofibrosis with myeloid metaplasia at diagnosis.…”

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confidence: 99%

JAK2V617F-positive polycythemia vera and Philadelphia chromosome-positive chronic myeloid leukemia: one patient with two distinct myeloproliferative disorders

et al. 2008

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Analysis of the exon 12 and 14 mutations of the JAK2 gene in Philadelphia chromosome-positive leukemia

Cited by 8 publications

References 7 publications

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1

Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1

The JAK2 exon 12 mutations: A comprehensive review

JAK2V617F-positive polycythemia vera and Philadelphia chromosome-positive chronic myeloid leukemia: one patient with two distinct myeloproliferative disorders

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