These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia.
DNA was available in 138 patients and mutation screening revealed 20 cases with JAK2, 6 with IDH, and 3 with MPL mutations; JAK2 and MPL mutations were seen mostly in MPN or "MDS with isolated del(5q)" whereas IDH mutations were frequent in other MDS variants.
We report a patient with a JAK2V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation.
JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, occurs in nearly all patients with polycythemia vera (PV) but also in a variable proportion of patients with other myeloid disorders; mutational frequency is estimated at approximately 50% in both essential thrombocythemia (ET) and myelofibrosis (MF), up to 20% in certain subcategories of atypical myeloproliferative disorder (atypical MPD), less than 3% in de novo myelodysplastic syndrome (MDS) or acute myeloid leukemia, and 0% in chronic myeloid leukemia (CML).
The JAK2V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes.
Herein, we describe the clinical, morphologic, immunophenotypic, cytogenetic, and molecular genetic findings in two MDS/AML cases that contained both MYC rearrangement and the JAK2V617F mutation.
Recently published studies report a small percentage of patients with RARS-T. Sixty percent of these have JAK2V617F mutation, which can suggest the coexistence of two pathological conditions (MDS and MPN).
The high frequency of myeloproliferative features and JAK2p.V617F mutation, and the low frequency of p53 dysregulation, suggest that fibrosis in the context of CMML has a different pathogenesis from that previously reported in myelodysplastic syndrome.
The JAK2-V617F mutation could be detected in 28 of 33 polycythaemia vera patients (85%), 29 of 49 essential thrombocythaemia patients (59%) and 2 of 6 IMF patients (33%), but was not detected in 11 patients with myelodysplastic syndrome or another 10 with other haematological diseases.
JAK2 mutation was also detected in 3 (19%) of 16 patients with Philadelphia-chromosome (Ph)-negative chronic myelogenous leukemia (CML), 2 (18%) of 11 patients with megakaryocytic AML, 7 (13%) of 52 patients with chronic myelomonocytic leukemia, and 1 (1%) of 68 patients with myelodysplastic syndromes.
To determine if JAK2V617F mutation is implicated in the abnormal thrombopoiesis of the 3q21q26 syndrome, we analyzed bone marrow samples of 12 patients, including 10 patients with acute myeloid leukemia and 2 patients with a myelodysplastic syndrome, associated with either inv(3)(q21;q26) or t(3;3)(q21;q26).
Although certain molecular defects are indicative of distinct cytogenetic abnormalities, others represent point mutations in critical target genes (RUNX1, N-RAS, JAK2, KIT, others) and sometimes are associated with a particular type of MDS, an overlap disease, a co-existing hematopoietic neoplasm or disease progression.
TET2 defects were observed in 15 of 81 patients with myelodysplastic syndromes (19%), in 24 of 198 patients with myeloproliferative disorders (12%) (with or without the JAK2V617F mutation), in 5 of 21 patients with secondary AML (24%), and in 2 of 9 patients with chronic myelomonocytic leukemia (22%).
Because detailed clinical and hematological characteristics of CBL-mutated cases is lacking, we screened 156 BCR-ABL and JAK2V617F negative patients with myeloproliferative neoplasms (MPN) and overlap syndromes between myelodysplastic syndrome (MDS) and MPN (MPS/MPN) for mutations in exons 8 and 9 of CBL by denaturing high-performance liquid chromatography and direct sequencing.
These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression.
We applied single nucleotide polymorphism arrays (SNP-A) to study karyotypic abnormalities in patients with atypical myeloproliferative syndromes (MPD), including myeloproliferative/myelodysplastic syndrome overlap both positive and negative for the JAK2V617F mutation and secondary acute myeloid leukemia (AML).