Chronic Myeloid Leukemia with a Complex Variant ‘Ph’ Translocation That Develops in Breast Carcinoma, Postchemotherapy: A Rare but Treatable Entity

Abstract

We report a case of chronic myeloid leukemia (CML) that developed after postoperative chemotherapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) for breast cancer. A 55-year-old woman was diagnosed with invasive ductal carcinoma which was treated with a modified radical mastectomy followed by six cycles of CAF chemotherapy. Nine years later, she developed CML and locoregional recurrence. Her breast recurrence showed strong estrogen receptor, weak progesterone receptor and strong human epidermal growth factor 2 (score 3+) expression. Her secondary CML in the chronic phase showed a complex variant translocation (CVT) involving chromosomes 9, 22, and 17. Considering that the HER2/neu gene is also located on chromosome 17, this secondary CML in chronic phase with CVT is indeed a rare occurrence. We discuss the associated genetic factors and the possible role of breast cancer chemo/radiotherapy in the development of such CML as well as its treatment and prognosis compared with de novo CML.

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 [9–16] .…”

“…[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. [9][10][11][12][13][14][15][16] Additionally, Al-Achkar et al [17] also reported a novel Ph chromosome-positive CML case lacking the BCR/ABL fusion gene on der(9) and instead harboring a new complex rearrangement formed by chromosomes 11 and 20, as well as 9 and 22.…”