A high proportion of cells carrying trisomy 12 is associated with a worse outcome in patients with chronic lymphocytic leukemia

Abstract

The prognosis of chronic lymphocytic leukemia (CLL) patients displaying trisomy 12 (+12) remains unclear. In this study, we analyzed the influence of the proportion of cells with +12, and other clinical and biologic factors, in time to first therapy (TTFT) and overall survival (OS), in 289 patients diagnosed with CLL carrying +12. Median OS was 129 months. One hundred seventy-four patients (60.2%) presented +12 in <60% of cells. TTFT and OS for this subgroup were longer than for the subgroup with +12 in ≥60% of cells, with a median TTFT of 49 months (CI95%, 39-58) vs 30 months (CI95%, 22-38) (P = 0.001); and a median OS of 159 months (CI95%, 119-182), vs 96 months (CI95%, 58-134) (P = 0.015). Other factors associated with a shorter TTFT were: Binet stage, B symptoms, lymphadenopathy, splenomegaly, high lymphocyte count, 11q-, high β2 microglobulin, and high LDH. In the multivariate analysis, clinical stage, +12 in ≥60% of cells, high lymphocyte count, B symptoms, and 11q- in addition, resulted of significance in predicting shorter TTFT. Significant variables for OS were: Binet stage, lymphadenopathy, splenomegaly, high LDH, high β2 microglobulin, 11q-, and CD38. In the multivariate analysis, only Binet stage, 11q-, and high β2microglobulin significantly predicted shorter OS. CLL with +12 entails a heterogeneous group with intermediate prognosis. However, a high proportion of cells carrying +12 separates a subgroup of patients with poor outcome. Copyright © 2015 John Wiley & Sons, Ltd.

Mutational status of IGHV is the most reliable prognostic marker in trisomy 12 chronic lymphocytic leukemia

“…Previous authors have demonstrated that a high proportion of cells bearing tris12 is associated with a worse outcome. 3,13 In the series herein, we could not confirm this feature, neither with tris12 evaluated as a continuous variable, nor as a dichotomous variable applying the cut-off point at 60% of tris12-bearing nuclei, as previously suggested.…”

“Immuno‐flowFISH” for the Assessment of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia

“…Prognosis in CLL can vary significantly depending on the genetic aberration which can have profound effects on overall survival and response to treatment (7). Trisomy 12, or the gain of one chromosome 12 (+12), is a cytogenetic aberration unique to CLL and is usually found in 10-20% of cases (8)(9)(10)(11)(12)(13)(14). Trisomy 12 cases are associated with an intermediate prognostic outlook and presence of this aberration does not alter disease management beyond the standard of care (11)(12)(13)(14)(15).…”

Two Distinct <b><i>BCL2</i></b> Rearrangements, Each Observed in 2 Independent Subclones, Evolving from a Founder Clone with Trisomy 12 in a Unique Case of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

“…Lau et al [11] reported a case of CLL with trisomy 12, t(14;18) ( IGH-BCL2 ), and t(8;14) (IGH-MYC) within the same clone, while Alpatov et al [9] reported a case of CLL with trisomy 12, t(14;18), and t(14;19) ( IGH-BCL3 ) within the same clone. In addition, 2 case series of CLL/SLL, harboring t(14;18) translocations also revealed trisomy 12 in approximately 13/22 (59%) and 6/12 (50%) cases, which is higher than the reported 15-20% observed in common CLL/SLL [4,10,12]. The biological basis for the association between trisomy 12 and t(14;18) has yet to be elucidated.…”

“…Cytogenetic aberrations observed in CLL/SLL provide valuable prognostic information including trisomy 12 and the deletions 13q14.3, 6q21, 11q22-23 ( ATM ), and 17p13 ( TP53 ) [1,2,3,4,5,6]. Importantly, CLL/ SLL can also acquire cytogenetic aberrations that result in clonal evolution and disease progression [7,8].…”