ABSTRACT
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.
Subject(s)
Mutation , Polycythemia Vera/genetics , Bone Marrow , Erythroid Precursor Cells , Erythropoietin , Humans , World Health OrganizationABSTRACT
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.
Subject(s)
Antineoplastic Agents/therapeutic use , Chromosomes, Human/genetics , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Benzamides , Chromosomes, Human, Pair 12/genetics , Chromosomes, Human, Pair 5/genetics , Chromosomes, Human, Pair 6/genetics , Female , Humans , Imatinib Mesylate , KaryotypingABSTRACT
BACKGROUND/AIM: Chronic myeloid leukemia (CML) represents a malignant myeloproliferative disease developed out of pluripotent hematopoietic stem cell that contains the fusion bcr-abl gene. Disorders that occur in the process of apoptosis represent one of the possible molecular mechanisms that bring about the disease progress. The aim of our study was to carry out the analysis of the presence of the amplification of the c-myc oncogene, as well as the analysis of the changes in the expression of Bcl-2 in the patients with CML. METHODS: Our study included 25 patients with CML (18 in chronic phase, 7 in blast transformation). Using an immunohistochemical alkaline phosphatase-anti-alkaline phosphatase (APAAP) method, we analyzed the expression of cell death protein in the mononuclear bone marrow cells of 25 CML patients. By a differential PCR (polymerase chain reaction) method, we followed the presence of amplified c-myc gene in mononuclear peripheral blood cells. RESULTS: The level of the expression of Bcl-2 protein was considerably higher in the bone marrow samples of the patients undergoing blast transformation of the disease. The amplification of c-myc gene was detected in 30% of the patients in blast transformation of the disease. CONCLUSION: The expression of Bcl-2 protein and the amplification of c-myc gene are in correlation with the disease progression.
