A rare case of three-way complex variant translocation in chronic myeloid leukemia t(6;9;22)(p21;q34;q11): A case report

Abstract

Abstract. Philadelphia (Ph)-positive chromosome or Ph translocation has been recognized in 90-95 chronic myeloid leukemia (CML) cases worldwide. However, only 5-8% CML patients show complex variant translocations. In the present study, hematological tests for a 47-year-old female CML patient were performed to determine the hemoglobin, platelets and total leukocyte values. A FISH test was carried out to recognize the BCR/ABL gene fusion, and a cytogenetic analysis was performed. The hematological results showed an increase in WBC (414000/mm 3 ) and a decrease in hemoglobin (8.9 mg/dl), indicating the anemic condition in the CML patient. Furthermore, cytogenetic karyotyping results showed 46,XX,t(6;9;22)(p21;q34;q11) and positive for Ph chromosome. In conclusion, in the present study, we report a rare three-way complex variant translocation in a CML patient. IntroductionThe clonal hematopoietic stem cell is associated with chronic myeloid leukemia (CML), which results due to the balance translocation among the long arms of chromosomes (9;22) (q34;q11) commonly known as Philadelphia (Ph) chromosome (1,2). CML consists of monocytic, megakaryocytic, myeloid, erythroid, B-lymphoid and T-lymphoid linkages (3). The nonfunctional crossbreed (PBCR-ABL) protein produced by the chimeric BCR-ABL gene with tyrosine kinase activity independently leads to myeloid proliferation and leukemic makeover (1,4). The translocation of chromosomes (9;22) (q34;p15) is perceived in almost 90-95% of patients with CML, and only 5-8% CML patients have established variant complex translocation, which is due to the participation of one or more chromosomes other than 9 and 22 chromosome (5-7).BCR-ABL protein tyrosine kinase is inhibited by the imatinib mesylate (IM), a conventional oral therapy for patients suffering from CML, irrespective of phases, with a response rate of 65-90% in CML cases. IM acts by blocking the production and inducing apoptosis of BCR-ABL gene expression in CML cells. It plays a vital role regarding continued survival and better quality of life (8-11).In the present study, we report a rare three-way Ph-positive complex variant translocation 46,XX,t(6;9;22)(p21:q34;q11) in a CML patient. Patient and methodsCase report. We report here a 47-year-old female patient who had established CML in Sundayman Civil Hospital (Quetta) on the 8th August, 2014. She was referred to the hospital because of symptoms including fever, anemia, weight loss, sweating, depression, swelling on the body and high blood pressure. The laboratory characteristics of the patient were WBC (414000/mm 3 ), hemoglobin (8.9 g/dl), platelets (619000/mm 3 ), MCV (56.2 FL), MCH (22.5/pg), lymphocytes (7%), neutrophils (20%), HCT (30.2%), monocytes (0.3%), MCHC (39.9 g/dl), metamyelocytes (33%), blast (2%), myelocytes (10%) and normoblasts (04/100 WBCs). The result of ultrasound report of the CML patient showed mild hepatomegaly and massive splenomegaly. The patient was treated with Glivec (imatinib) 600 mg/day. Approval for the study was obtained from the Ethics...

Management of chronic myeloid leukemia presenting with isolated thrombocytosis and complex Philadelphia chromosome

“…CML is characterized by the genetic translocation, t (9; 22) (q34; q11.2), that results in the fusion of Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. [ 5 , 6 ] The Philadelphia chromosome translocation is observed in 90% to 95% of CML patients whereas more, complex translocations, involving a third chromosome are present in only 5% to 8% of the patients. [ 7 , 8 ] Although variant translocations might involve any chromosome, the distribution of the breakpoints is nonrandom and, usually seen at some specific chromosomal bands, including 1p36, 2p22,3p21, 4q25,5q31, 6p21, 9q22, 10q22, 11q13, 12p13, 16p13,17p13,17q21, 17q25, 19q13, 21q22, 22q12, and 22q13.…”

Recurrent chronic myeloid leukemia with t (9;22;16) (q34; q11; p13) treated by nilotinib

“…[ 15 ] Imatinib acts by blocking BCR-ABL gene expression and inducing apoptosis of CML cells, playing a vital role in continued survival and better quality of life. [ 5 ] Although initial response is high, therapy fails in up to 40% of patients and initial response is lost within 2 years in approximately 25% of patients with t (9;22) (q34; q11) translocation. [ 16 ] In another study, it was found that the patients with complicated differentiated disposal Ph positive CML showed a poorer prognosis after treatment with imatinib.…”

“…Around 5% to 10% of these patients show complex translocations involving a third chromosome in addition to chromosomes 9 and 22. [ 4 , 5 ] Extra Ph, +8, i(17q) and +19, have been described as the most common secondary changes (known as the major route), whereas others infrequent changes are considered the minor route. [ 6 ] Here, we report a recurrent, complicated, differentiated case of CML with t (9,22,16) (q34; q11; p13) which was treated by nilotinib, a second-generation tyrosine kinase inhibitor (TKI).…”

Three-way Complex Variant Translocation Involving Long Arm of Chromosome 1 in a Chronic Myeloid Leukemia Patient

“…They suggested identified translocation to be associated with poor prognosis in CML patients if treated with imatinib [10]. Involvement of chromosomes 7 and 17 is also documented in literature in cases of three way translocations [11,12].…”