Fluorescence in situ hybridization in conjunction with karyotyping in detection of cytogenetic abnormalities in B-cell chronic lymphocytic leukemia and its prognostic value

ABSTRACT

Routine cytogenetic analysis frequently fails to identify an abnormal clone in B-cell lymphocytic leukemia [B-CLL] due to poor response to mitogen stimulation. Fluorescence in situ hybridization [FISH] suggest that chromosomal abnormalities occur more frequently, most commonly trisomy 12, retinoblastoma gene deletion [Rb 1 gene] and P53 gene deletion. 30 patients with B-CLL were enrolled in the trial from 2 centers in Cairo, Egypt during the period May 2000 to January 2002. Karyotyping and FISH assessment for possible chromosomal abnormalities [trisomy 12, Rh 1 gene and P53 gene] were done at initial diagnosis. Results of cytogenetic abnormalities were correlated with clinical picture and survival. The median age was 57.4 years [range 40-75]. Karyotyping technique showed that no metaphase could be detected in 30%, metaphase with normal karyotyping was observed in 63% and cytogenetic abnormalities were detected in 2 cases [1 trisomy 12 and 1 deletion in chromosome 13]. FISH examination of interphase and metaphase nuclei revealed cytogenetic abnormalities in 15 cases [50%], trisomy 12 in 9 [30%], Rb 1 gene deletion in 5 [17%] and P53 gene deletion in 1. At diagnosis, patients with trisomy 12 were significantly associated with advanced stage and absolute lymphocyte count of >/= 30,000/mm[3]. Univariate analysis showed that absolute lymphocyte count >/= 30,000/mm[3] [p=0.004] and trisomy 12 [p=.024] were associated with poor progression free survival. Interphase and metaphase FISH studies improve the cytogenetic diagnosis of chromosomal abnormalities in B-CLL. Lymphocytosis and trisomy 12 might be a good indicator of poor prognosis