MYC translocation in chronic lymphocytic leukaemia is associated with increased prolymphocytes and a poor prognosis

Abstract

SummaryChromosomal translocations that involve MYC, characteristic of Burkitt lymphoma, are rare in chronic lymphocytic leukaemia (CLL). We report the clinical, morphological, immunophenotypic, cytogenetic and molecular genetic features of eight CLL cases with MYC rearrangement. The patients, five men and three women (median age, 71 years) had bone marrow involvement and an absolute peripheral blood lymphocytosis; five had lymphadenopathy; seven had splenomegaly. Prolymphocytes were increased (≥10%) in all cases. Six cases were classified as CLL with increased prolymphocytes (CLL/PL; prolymphocytes 10–55%), and two were classified as CLL in prolymphocytic transformation (CLL/PT; prolymphocytes >55%). All cases co‐expressed CD5, CD19, and CD23; five of eight expressed ZAP‐70. Of seven cases tested, four had mutated and three had unmutated IGHV genes. Conventional cytogenetic studies demonstrated t(8;14)(q24·1;q32) in five cases, t(8;22)(q24·1;q11) in two cases, and t(2;8)(p12;q24·1) in one case. Seven cases contained additional chromosomal abnormalities. All patients received combination chemotherapy. Two developed Epstein–Barr virus (EBV)‐associated diffuse large B‐cell lymphomas (DLBCL) that were clonally unrelated to the CLL. At follow‐up, two patients are alive, four died of underlying disease, one died of EBV‐associated DLBCL, and one died of an unrelated cancer. In summary, MYC rearrangement, which occurs rarely in CLL patients, is associated with increased prolymphocytes, complex cytogenetic abnormalities, and a poor prognosis.

B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia

“…Chromosomal alterations resulting in increased expression of c-MYC also were found in other B-cell malignancies, including diffuse large B-cell lymphoma (2) and multiple myeloma (3). In rare cases of chronic lymphocytic leukemia (CLL), c-MYC translocations were found associated with progressive disease and poor prognosis (4).…”

The clinical significance of 8q24/MYC rearrangement in chronic lymphocytic leukemia

“…8q24/MYC rearrangement was detected at time of initial diagnosis of chronic lymphocytic leukemia in three patients (case 1,5,8), and detected during the course of disease in 17 patients. Of the latter 17 patients, 5 were on observation only and 12 had received various treatments for chronic lymphocytic leukemia (Table 1), and 8q24/MYC rearrangement was detected after a median interval of 48 months (range 4-186 months) after diagnosis.…”

“…Of note, six of these patients (cases 4-5, 14-17) have been reported previously. 8 Seven patients had karyotypic information available prior to detection of 8q24/MYC rearrangement. Of those, three patients (cases 10, 13, 16) showed t(8q24;v) arrangements as a result of clonal evolution (case 10 showed a normal karyotype, but FISH detected +12 at the time of diagnosis), and two (cases 9, 17) as new clones (Table 2).…”

“…Prolymphocytes in peripheral blood were increased in nine patients, five with prolymphocytes of 10~34% (chronic lymphocytic leukemia with increased prolymphocytes), and four had prolymphocytes 455% (chronic lymphocytic leukemia in prolymphocytoid transformation) ( Table 1). All patients showed an increased serum B2 microglobulin level (median 4.6 mg/l, range 2.1-11.2 mg/l) (reference range, 0.7-1.8 mg/l) and 17 (cases [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] had an increased serum lactate dehydrogenase level (median 1220 IU/l range 507-19328 IU/l) (reference range, 313-618 IU/l). Rai stage was IV in nine patients, III in four patients, II in six patients, and 0 in one patient.…”

“…7 8q24/MYC rearrangement is rare in chronic lymphocytic leukemia and only occasional cases have been reported. [8][9][10][11][12][13][14][15][16][17] In most of these reports, 8q24/MYC rearrangement occurred as a part of a complex karyotype, often associated with increased prolymphocytes or Richter's transformation and an aggressive clinical course; only rare cases reported had typical chronic lymphocytic leukemia morphology and responded well to chemotherapy. 5,9 To better characterize the clinical behavior and pathological features of chronic lymphocytic leukemia with 8q24/MYC rearrangement, we searched our database for all chronic lymphocytic leukemia patients at our institution in the past 15 years, and identified 20 patients with 8q24/MYC rearrangement who had detailed clinical, pathological, and cytogenetic information available.…”