Investigation of the CCND1 gene in a variant t(9;22;11)(q34;q11.2;q13) chronic myeloid leukemia. I. Yudelman¹, M.J. Macera^2,3, R. Zeng^2,3, J. Breshin^2,3, P. Chandra³, A. Babu^2,3. 1) Dept Medicine, Lenox Hill Hospital, New York, NY; 2) Div Molec Medicine & Genetics; 3) Dept Medicine, Wyckoff Heights Medical Ctr, Brooklyn, NY.
   Five to ten percent of all Ph positive cases have a variant translocation and involves at least one additional chromosome in the rearrangement. There have been a number of studies done to determine prognostic value of the variant' translocation in response to Gleevec therapy. There appears to be no prognostic difference in the two groups. Recently, it has been described that some CML patients have a deletion in the 5 ABL1 gene and/or the 3 BCR gene. It has been reported that such deletions may have a survival disadvantage. Approximately 10% of the typical t(9;22) cases were shown to have a deletion in ABL and/or BCR; deletions are more frequent in the variant cases (up to 40%), some with deletions in the additional chromosome involved. A variant translocation, 46,XY,t(9;22;11)(q34;q11.2;q11), was seen in a patient referred for CML. FISH with a dual color-dual fusion BCR/ABL probe showed three signals of ABL1 (ABL1 x3) and three signals of BCR (BCR x3) with a single fusion of BCR/ABL (ABL1 con BCR x1). A second fusion was not seen as the 3BCR translocated to 11q13. The BCR/ABL1 probe showed no loss of signal and, therefore, no detectable deletion. The chromosome region 11q13 is the second most frequent in variant translocations. Oncogene cyclin D1 (CCND1/BCL1) is located in 11q13. To determine the role, if any, and location of the cyclin D1 oncogene and detect any loss of chromosome material, the CCND1/MYEOV break-apart probe was applied. The entire CCND1/MYEOV probe was translocated to the der(9), suggesting that the breakpoint is proximal to CCND1. No deletions at the breakpoints of this translocation were detected by this probe. The patient was treated with a standard Gleevec therapy and has shown a complete hematological response and a partial cytogenetic response. It is becoming clear that although there appears to be a higher percentage of variant translocations with deletions at the breakpoints, additional data will help to delineate clinical response in these patients.