Four novel non‐random chromosome rearrangements in B‐cell chronic lymphocytic leukaemia: 6p24–25 and 12p12–13 translocations, 4q21 anomalies and monosomy 21

Abstract

Summary. Nine patients with previously unreported chromosome changes were identi®ed among 209 B-cell chronic lymphocytic leukaemia (CLL) cases: three patients had a translocation involving 6p24±25; three had a 12p12±13 translocation; two had 4q21 involvement (one with coexisting 6p anomaly); and two had monosomy 21.Interphase¯uorescence in situ hybridization (FISH) detected some cryptic aberrations (12, 6q±, 17pÀ, 11qÀ) in those patients with 6p translocations, whereas only a cytogenetically undetected 13q14 deletion was found in the remaining cases.Atypical morphology was noted in six cases, including both cases with monosomy 21, two cases with 6p and 4q21 anomaly and one case with 12p involvement. Four of these cases also had more than one phenotype deviation with respect to the classical CLL phenotype. Disease progression after 21±51 months (median 41) was noted in two cases with 6p and 4q21 involvement and in one case with 12p anomaly and monosomy 21.We arrived at the following conclusions: (i) 6p24±25 and, possibly, 4q21 lesions represent non-random events in CLL, occurring in association with other well-known unbalanced rearrangements; (ii) 12p rearrangements and monosomy 21 may possibly represent early chromosome defects that are not associated with the classical DNA gains and losses known to be present in the majority of CLL; and (iii) atypical morphology and immunophenotype as well as disease progression were frequently observed in these cases

Structural aberrations of chromosomes 17 and 12 in chronic B‐cell disorders

“…Recently, 12p aberrations, as a possible primary anomaly in CLL, have been reported. Interestingly, an aggressive clinical course was observed in one of those cases with isolated 12p involvement (34). In concordance with this finding, our patient was refractory to chemotherapy and died because of disease progression, 9 months after the SLL diagnosis.…”

Chronic lymphocytic leukemia with 6q− shows distinct hematological features and intermediate prognosis

“…In a molecular genetic study, allelic loss at 6q was detected in up to 15% of informative CLL patients, showing that 6q deletion may be an important event in the molecular pathogenesis of some CLL cases. 33 Interestingly, recurrent chromosome aberrations were recently described in CLL that were not associated with the classical 13qÀ, 17pÀ, 11qÀ, þ 12 anomalies, 15 suggesting that a distinct minority of CLL cases may develop through novel cytogenetic routes. …”

“…17 The 6qÀ anomaly did not appear to influence survival in previous studies. 5,15,13 An association was found between 6qÀ and a high white blood cell (WBC) count, more extensive adenopathy at presentation 15 and shorter treatment-free interval (TFI). 18 The latter finding, however, was not confirmed in another study, 16 showing no difference in terms of clinical behavior between CLL with and without 6qÀ.…”

“…14 Given the importance of recognizing correlations between cytogenetic and clinicobiological features in CLL, the significance of novel recurring aberrations is currently under scrutiny. 15 The 6qÀ chromosome is know to occur at a relatively low frequency in CLL, having been reported in 3-6% of the cases by CCA and by FISH, 7,16 mostly as a secondary chromosome anomaly or in the context of complex karyotypes. 17 The 6qÀ anomaly did not appear to influence survival in previous studies.…”

MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B‐Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

“…We, therefore, examined whether MUM1 expression in B-CLL cell lines was due to deregulated expression as a result of t(6;14)(p25;q32), as is the case with multiple myeloma, since Cuneo et al 41) recently reported that the 6p24-25 locus was occasionally involved in non-random rearrangements in B-CLL cases. However, this hypothesis was refuted by the results of the DCFISH analysis of two B-CLL cell lines expressing MUM1.…”