JAK2V617F mutation and endogenous erythroid colony formation in patients with polycythaemia vera.

PURPOSE: The purpose of this study was to investigate the frequency of JAK2V617F gene mutation in patients with polycythemia vera (PV) and to compare the results with the presence of endogenous erythroid colony (EEC) formation. METHODS: Peripheral blood and bone marrow samples of 28 patients with PV were analyzed. The diagnosis of PV was established according to the bone marrow criteria of the World Health Organization (WHO). Mutation of JAK2V617F was determined by allele-specific PCR (AS-PCR) analysis. For detection of EEC formation we used assays of human clonogenic heamatopoietic progenitor cells with agar-leukocyte conditioned medium (Agar-LCM) without recombinant human erythropoietin (EPO). RESULTS: Mutation was found in the samples of the peripheral blood in 26/28 (92.9%) PV patients. EEC formation was obtained in the sample of bone marrow in 27/28 (96.4%) PV patients. In 25/28 (89.2%) patients we detected presence of EEC formation and mutation of JAK2V617F at the same time. CONCLUSION: Considering these results, we hypothesized that the EEC formation observed in myeloproliferative disorders could be partially due to the JAK2-dependent activation signaling pathway.

Allogeneic stem cell transplant for chronic myeloid leukemia as a still promising option in the era of the new target therapy.

BACKGROUND/AIM: Introducing tyrosine kinase inhibitors (TKIs) has essentially changed curative approach, to be precise, clearly improved treatment efficacy for chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem cell transplant (SCT) in CML treatment--as a former "nearly monopolistic" therapeutic manner--is nowadays controversial. The objective of this retrospective study was to evaluate the results obtained in the treatment of CML patients, with a particular attempt to define parameters critical for clinical benefit and superior overall outcome following allogeneic SCT. METHODS: A total of 32 CML patients (27 in chronic phase and 5 with advanced disease), with female/male ratio 11/21, aged from 9 to 54 (32 in average) years, underwent allogeneic SCTs (1993 to 2009). The initial treatment for 25 patients was interferon alpha (IFN-alpha) with or without ARA-C, and additional 7 patients with no response to imatinib mesylat (IM). The time from diagnosis to SCT was approximately 12 (range 3-37) months. The patient were categorized according to the risk for the disease, transplant-related mortality (TRM) scoring system, and stem cell (SC) source. The basic conditioning regimen was a combination of busulphan and cyclophosphamide (BuCy-2). Graft-versus-host disease (GvHD) was typically prevented with cyclosporine-A (CsA) and methotrexate (MTX). RESULTS: Engraftment was observed in 26 (84.4%) patients, with polymorphonuclear (PMNs) and platelet (Plt) recovery on the 15th (range 10-22) and 19th (range 11-29) posttranspalnt days, respectively. Acute GvHD (aGvHD) had 13/26 (50%), and chronic GvHD (cGvHD) 10/21 (47.1%) patients. The incidence of overall TRM was 46.8% (15/32), while early death was noticed in 4 (12.5%) patients. A cause of death in 9 (28.1%) patients was cGvHD, in 2 (6.25%) patients infection, and in 3 (9.35%) cases disease-relapse was occurred. Fourteen (43.7%) of the patients are still alive, 9 from the low-risk group for TRM, with long-term survival from 1 to 16 years. Patients who received SCs from peripheral blood (PB) vs bone marrow (BM) had significantly faster engraftment (p < 0.05), lower oropharingeal mucositis rate (25% vs 70%; p < 0.05), but more frequent cGvHD (83.3% vs 30.3%; p < 0.05). A significantly improved (log-rank = 2.39; p < 0.01) overall survival (OS) was obtained in BM-setting. CONCLUSION: The results obtained in this study are in accordance with data from analogous clinical trials. Exactly, in the era of the new target therapy (TKI application), allogeneic SCT can be still a convenient therapeutic approach for well-selected CML-patients, especially for those with initial high-risk disease and lower probability of TRM.

t(5;6;12) associated with resistance to imatinib mesylate in chronic myeloid leukemia.

A patient with t(9;22)-positive chronic myelogenous leukemia (CML) developed a resistance to therapy with imatinib mesylate (Glivec) which coincided with the appearance of t(5;6;12) in the same cells with t(9;22) [46,XX,t(5;6;12)(q14?;q21?;q23?),t(9;22)(q34;q11)]. She remains in a continuous chronic phase of CML. This is the first reported instance of karyotype evolution temporally associated, and possibly involved, with the induction of resistance to imatinib mesylate but without any signs of evolution of leukemia toward a more anaplastic and aggressive form.

A Ph-negative chronic myeloid leukemia with a complex BCR/ABL rearrangement and a t(6;9)(p21;q34.1).

Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoetic stem cell characterized by the presence of the Philadelphia (Ph) chromosome in more than 90% of patients. Cryptic or "masked" BCR/ABL gene rearrangements may be found in cases with a normal karyotype and in cases with the complex karyotype, in which typical t(9;22) is not visible at the microscopic level. Those rearrangements can now be detected by fluorescence in situ hybridization. Here, we report on a novel and complex Ph chromosome-negative CML case with a t(6;9)(p21;q34.1) in which the BCR/ABL fusion gene is located at 6p21.