CYTOGENETIC AND INTERPHASE CYTOGENETIC CHARACTERIZATION OF ATYPICAL CHRONIC LYMPHOCYTIC-LEUKEMIA CARRYING BCL1 TRANSLOCATION

Conventional chromosome analysis (CCA) and fluorescent in situ hybridi zation (FISH) studies, using a 390-kb yeast artificial chromosome prob e spanning the area of multiple breakpoints of the BCL1 locus at 11q13 , were performed on 57 patients fulfilling the French-American-British criteria for the diagnosis of atypical B-cell chronic lymphocytic leu kemia (CLL). To better define the incidence of 13q deletions and triso my 12, FISH analysis was also performed using a cosmid probe that reco gnized a DNA sequence between the Rb gene and the D13S25 locus at band 13q14 and a chromosome 12-specific pericentromeric probe. All patient s were characterized by cytoimmunological and hematological studies, F ourteen cases displayed three fluorescent signals in 41-98% interphase cells when hybridized to the BCL1 yeast artificial chromosome probe, documenting the presence of BCL1 translocation (BCL1-positive cases), The presence of t(11;14)(q13;q32) was ascertained in 12 cases using CC A and by dual color interphase FISH using the BCL1 probe and a 14q tel omere probe in 2 karyotypically normal cases, The remaining 43 cases h ad two signals in more than 95% interphase cells (BCL1-negative) and d id not have the t(11;14) at CCA, Although 13q14 deletions were seen by means of CCA in only 5 of 14 BCL1-positive cases, hemizygous or homoz ygous deletions at band 13q14 were detected by FISH in 11 of 14 BCL1-p ositive cases, as compared with 17 of 43 BCL1-negative cases (P = 0.01 ), A subclone with trisomy 12 in addition to BCL1 translocation and de l(13q14) was present in four BCL1-positive cases, We arrived at the fo llowing conclusions: (a) FISH with this BCL1 YAC probe is an efficient method for the detection of the t(11;14) and of the corresponding inv olvement of the BCL1 locus in this lymphoproliferative disorder; (b) t he majority of BCL1-positive atypical CLLs by French-American-British criteria may carry 13q14 deletions; (c) the recognition of this cytoge netic subset of atypical CLL, sharing some immunological and cytogenet ic features with mantle cell lymphoma, may be important, because these patients usually present isolated peripheral blood and marrow lymphoc ytosis, with or without mild to moderate spleen involvement, and may r equire early cytotoxic treatment.