Chronic lymphocytic leukemia and prolymphocytic leukemia with MYC translocations: a subgroup with an aggressive disease course

Abstract

Translocations involving MYC are rare in chronic lymphocytic leukemia (CLL), and up to now, their prognostic significance remains unclear. We report the characteristics of 21 patients with CLL and nine patients with prolymphocytic leukemia (PLL), diagnosed in multiple centers (n = 13), which showed an MYC translocation demonstrated by fluorescence in situ hybridization. The prevalence was estimated to be <1%. Advanced age and male predominance were observed. Morphological analysis frequently revealed the presence of prolymphocytes. A typical "CLL-immunophenotype" was found in four of nine cases with PLL. Moreover, CD5 and CD23 were frequently expressed in PLL. The latter findings are atypical for PLL and may suggest transformation or progression of an underlying CLL. MYC translocations were frequently observed with concomitant adverse cytogenetic markers, such as del(11q) (n = 8/30) and/or del(17p)/monosomy 17 (n = 7/30). In addition, the presence of unbalanced translocations (n = 24 in 13/30 cases) and complex karyotype (n = 16/30) were frequent in cases with MYC translocations. Altogether, del(17p)/monosomy 17, del(11q), and/or complex karyotype were observed in 22 of 30 patients. Survival outcome was poor: the median time to treatment was only 5 months, and overall survival (OS) from clinical diagnosis and from genetic detection was 71 and 19 months, respectively. In conclusion, CLL/PLL with MYC translocations is a rare entity, which seems to be associated with adverse prognostic features and unfavorable outcome.

Immunoglobulin gene translocations in chronic lymphocytic leukemia: A report of 35 patients and review of the literature

“…Put et al (70) reported a prevalence of del(11)(q22) and del(17)(p13) in a cohort of 25 patients with a t(8;14) or variants, which was higher compared with that reported in CLL [6̸25 (24%); and 7̸25 (28%), respectively] (70).…”

“…This abnormality is rare in typical CLL and is associated with increased PLs (CLL with occasional PLs, CLL/PL and PLL) (68)(69)(70)(71). Male and elderly patients are predominantly affected, as in CLL/PL patients (69)(70)(71).…”

“…It is usually included in a complex karyotype. It may represent a secondary abnormality contributing to disease progression and carries a poor prognosis (68)(69)(70).…”

Genetics of Chronic Lymphocytic Leukemia: Practical Aspects and Prognostic Significance

“…Similarly, translocations involving MYC have been associated with loss (i.e. monosomy) of 17, del(11q) complex karyotype, additional unbalanced translocations and poor prognosis (Put et al, 2011). In contrast, translocations involving BCL2 are associated with mutated IGVH genes, trisomy 12, absence of del(11q) and more favorable outcome (Put et al, 2009b).…”

MYC as therapeutic target in leukemia and lymphoma

“…52 Amplification and rearrangements of MYC are rare in CLL (less than 3%), but when they occur, they correlate with a poor prognosis and aggressive disease. [53][54][55] Also, in CLL transformation to high-grade lymphoma, known as Richter syndrome, MYC upregulation is frequent, similar to other aggressive lymphomas. 54,56 Thus, MYC gene abnormalities in low-grade lymphomas are usually secondary events that frequently appear in an event of progression or transformation, and thus are associated with an adverse prognosis.…”