Improved diagnosis of the transition to JAK2 (V⁶¹⁷F) homozygosity: the key feature for predicting the evolution of myeloproliferative neoplasms.

Most cases of BCR-ABL1-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera and primary myelofibrosis are associated with JAK2 (V617F) mutations. The outcomes of these cases are critically influenced by the transition from JAK2 (V617F) heterozygosity to homozygosity. Therefore, a technique providing an unbiased assessment of the critical allele burden, 50% JAK2 (V617F), is highly desirable.

BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia.

BCR-ABL fusion gene is implicated in the pathogenesis of chronic myeloid leukemia (CML), encoding the oncoprotein p210(BCR-ABL) with anti-apoptotic activity. The inability to undergo apoptosis is an important mechanism of drug resistance and neoplastic evolution in CML. The gene transcript expression of mitochondrial apoptotic related genes BAX and BCL-XL was evaluated by quantitative Real Time PCR (qPCR) in vitro in K562 cells and in vivo in peripheral blood of 66 CML patients in different stages of the disease: 13 cases at diagnosis, 34 in chronic phase (CP), 10 in accelerated phase (AP) and 9 in blast crisis (BC).

Caffeic Acid Phenylethyl Ester and MG-132 Have Apoptotic and Antiproliferative Effects on Leukemic Cells But Not on Normal Mononuclear Cells.

Chemotherapy aims to limit proliferation and induce apoptotic cell death in tumor cells. Owing to blockade of signaling pathways involved in cell survival and proliferation, nuclear factor kappaB (NF-kappaB) inhibitors can induce apoptosis in a number of hematological malignancies. The efficacy of conventional chemotherapeutic drugs, such as vincristine (VCR) and doxorubicine (DOX), may be enhanced with combined therapy based on NF-kappaB modulation.

Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients.

Imatinib mesylate has proven to be the most effective treatment in chronic myeloid leukemia. Nevertheless, imatinib resistance has raised concern and prompted interest in additional strategies to achieve disease eradication. Resistance to imatinib is mainly associated with three mechanisms: acquired mutations in the kinase domain of BCR-ABL protein, genetic amplification, and transcript overexpression of BCR-ABL rearrangement.

Chronic lymphocytic leukemia developing in a patient with chronic myeloid leukemia: evidence of distinct lineage-associated genomic events.

We describe the cytogenetic, fluorescence in situ hybridization (FISH), and molecular findings in a patient who developed a typical chronic lymphocytic leukemia (CLL) 20 months after the diagnosis of a Philadelphia (Ph)-positive chronic myeloid leukemia. Unstimulated bone marrow culture showed a 46,XX,t(9;22)(q34;q11) karyotype, and interphase FISH detected the presence of a BCR/ABL fusion signal in 13% of cells. On stimulated bone marrow culture, a normal karyotype and a 13q14 deletion by interphase FISH with D13S319 probe in 14% of the cells were found.

Insertion (4;11)(q27;q24q21) in a patient with essential thrombocythemia with progression to myelofibrosis.

We report a case of essential thrombocythemia (ET) in a 39-year-old woman who developed myelofibrosis at follow-up. The cytogenetic and fluorescence in situ hybridization analyses revealed a pathologic clone with the following previously unreported karyotype: 46,XX,ins(4;11)(q27;q24q21). We cannot conclude that the presence of this inverted insertion was associated with the overproduction of platelets, but documentation of more cases with chromosomal abnormalities and ET should lead to identifying different candidate genes involved in the neoplastic growth.

Amplification of the BCR/ABL fusion gene clustered on a masked Philadelphia chromosome in a patient with myeloblastic crisis of chronic myelocytic leukemia.

Although the chronic phase of chronic myelocytic leukemia (CML) is characterized by the Philadelphia (Ph) chromosome creating a hybrid BCR/ABL gene, additional genetic changes involved in blast crisis are poorly understood. We report a 4-8-fold amplification by tandem duplication of the BCR/ABL fusion gene clustered on a masked Ph chromosome in a 61-year-old male patient with CML in myeloblastic crisis. Our finding suggests that the BCR/ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Ph-positive CML.