No Evidence for JAK2^V617F Mutation in Monoclonal B Cells in 2 Patients with Polycythaemia Vera and Concurrent Monoclonal B Cell Disorder

Abstract

Occurrence of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph^– MPN) and lymphoproliferative disorders, like B cell chronic lymphocytic leukaemia (B-CLL), in the same patient is rare. JAK2^V617F mutation was recently introduced as a powerful diagnostic tool for Ph^– MPN. JAK2^V617F mutation is not present in B-CLL. In 4 previously reported patients with JAK2^V617F-positive Ph^– MPN and B-CLL there was no definitive proof of JAK2^V617F mutation in B-CLL cells, although this was suggested in 1 patient. We present 2 patients with JAK2^V617F-positive polycythaemia vera who subsequently developed a monoclonal B cell disorder. The granulocytes were separated from the mononuclear cells by centrifugation on density gradient. Using an ARIA-SORP sorter, the CD20+/CD5+ B cells were separated from the CD20+/CD5– B cells, T cells, NK cells and monocytes. On each of the fractions JAK2^V617F mutation was analysed by allele-specific competitive blocker-PCR. In both patients JAK2^V617F mutation was present in granulocytes confirming the clinical diagnosis of polycythaemia vera. We did not detect the JAK2^V617F mutation in the CD20+/CD5+ B cells but detected it in CD20+/CD5– B cells, T and NK cells, indicating a lymphoid subdifferentiation of the JAK2^V617F MPN clonality. JAK2^V617F MPN and monoclonal B cell disorder can coexist but there is no evidence that the proliferative behaviour of these B cells is mediated through the JAK2^V617F mutation.

Extinction of myeloproliferative neoplasm by acquisition of a lymphoid disease: JAK2 V617F and JAK2 exon 12 allele burden disappearance during the follow-up of two patients

“…Interestingly, cytoreductive treatment for MPN had no impact on lymphoid cells counts and reciprocally [6]. In subsequent studies, authors showed that cells of myeloid and Blymphoid diseases did not harbor common mutations [7]. Of note, to the best of our knowledge, this is the first report of an association between a mutation of the exon 12 of JAK2 and a CLL.…”

JAK2 V617F detected in two B-cell chronic lymphocytic leukemia patients without coexisting Philadelphia chromosome-negative myeloproliferative neoplasms: A report of two cases

“…Of the 28 cases of JAK2 V617F-positive B-CLL patients reported in the literature (Table 1) (6–15), the male and female ratio was 1.6:1 (17 males vs. 11 females), the median age of the males was 69 years (range, 55–94 years) and was 74 years (range, 58–82 years) for the females. In total, 27 patients exhibited coexistent Ph-MPN (essential thrombocythemia, n=16; polycythemia vera, n=10; and idiopathic myelofibrosis, n=1).…”

“…This mutation has also been identified in a small number of other myeloid malignancies (2,3), however, rarely presents in lymphoid malignancies (4,5). Following a search of the English language literature between 2006 and January 2013 using the search terms ‘B-cell lymphocytic leukemia’ (B-CLL) and ‘JAK2’, 28 JAK2 V617F-positive B-CLL patients were identified (6–15). All of these patients exhibited a Ph-MPN concomitantly.…”

Mutations and chromosomal rearrangements ofJAK2: not only a myeloid issue

“…At the same time also CD20 + /CD5 -B cells, T cells and NK were found JAK2V617F positive while the mutation was not detected in the CD20 + /CD5 + B cells. On the base of these results, the author concludes that there is no evidence that the proliferative behavior of B cells is mediated by the JAK2V617F mutation even if the B-CLL and the JAK2V617F-positive MPN do coexist [64]. On the contrary, Kodali et al reported a case of one patient who had both a JAK2-mutated MPN and B-CLL and studied the status of the mutation in stem cells, myeloid and lymphoid cell lines.…”

“…Negative in CD5+ B lymphocytes PV [64] 3 Negative PV [63] 1 Negative ET The clinical and hematologic data refer to the time when the peripheral blood was collected and analyzed for the JAK2V617F mutation. B-CLL: B-cell chronic lymphocytic leukemia; M: Male.…”