Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients

Abstract

Objective: The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations. Materials and Methods: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. Results: Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15) (q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22) (q11;q13;q34;q11). Conclusion: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3)(q24;q34;q11;q21) apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22)(q11;q13;q34;q11) full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients. (Turk J Hematol 2011; 28: 186-92)

A rare case of a three way complex variant positive Philadelphia translocation involving chromosome (9;11;22)(q34;p15;q11) in chronic myeloid leukemia: A case report

“…BCR/ABL interferes with the function of white blood cells, making it challenging for the body to fight off infections. The Ph chromosome (9;22)(q34;q11) is found in 90-95% of CML patients; however, only 5-8% of CML patients demonstrate a variant that involves a third chromosome other than (9;22) in a three-way Ph chromosome complex (1,8,17).…”

“…However variant or complex translocations involving one or more additional chromosomes compared with (9;22)(q34;q11) may be observed in 5-8% CML patients (1,7,8).…”

“…CML is caused by reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11), termed the Philadelphia chromosome (Ph) (1,2). The translocation consists of the combination of the break-point cluster region (BCR) and Abelson (ABL) genes to form the fusion gene BCR/ABL, which produces a chimeric protein with deregulated tyrosine kinase activity.…”

Cytogenetical and hematological analysis of chronic myelogenous leukemia patients with a novel case 52XX, t (1;9;22) (q23.3; q34; q11.2), +6, +8, i(9) (q10;q10), +18,+19,+21+der22 t(9;22)(q34;q11)

“…On the other hand variant/complex translocations including one or more additional chromosomes instead of (9; 22)(q34; q11) were perceived only <8% of CML patients. [1,3,4] However genetic additional abnormalities happen in <10% of chronic myeloid leukemia Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.…”

Precursor B cell lymphoid blast crisis of chronic myeloid leukemia with novel chromosomal abnormalities: A case report

“…CML is a myeloproliferative disorder that is characterized by the presence of the reciprocal translocation t(9;22), which forms the Philadelphia (Ph) chromosome. During this translocation, the breakpoint cluster region (BCR) gene at position 22q11.2 is juxtaposed to the c-Abelson (ABL1) gene at 9q34.1, forming the BCR-ABL1 fusion gene, which encodes a constitutively active tyrosine kinase (TK) protein (1,2). The constitutively active protein is associated with increased levels of erythrocytes, monocytes, megakaryocytes, myelocytes and platelets in the peripheral blood and marked myeloid hyperplasia in the bone marrow (3).…”