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Significance of Interphase Fluorescence in situ Hybridization (I-FISH)on Examination of Patients with Chronic Lymphocytic Leukemia (CLL)


Authors: K. Michalová 3;  Z. Zemanová;  E. Cmunt;  J. Karban
Authors‘ workplace: III. interní klinika VFN a 1. LF UK 2 I. interní klinika VFN a 1. LF UK 3 Ústav hematologie a krevní transfuze, Praha 1
Published in: Čas. Lék. čes. 2000; : 334-338
Category:

Overview

Background.
Trisomy 12 was found to be the most frequent chromosomal aberration identified by conventionalcytogenetic studies of bone marrow cells and peripheral lymphocytes of patients with CLL. Molecular-cytogenetictechniques which enable examination of dividing and/or non-diving interphase nuclei (I-FISH), proved existence ofother chromosomal abnormalities, mainly deletions, which could have in CLL patients relation to the origin, courseand prognosis of the disease.Methods and Results. During the last two years bone marrow chromosomes of all patients with CLL wereexamined by G-banding and by I-FISH. The numerical changes of chromosome 12 were followed by centromericDNA probe in dividing and non-dividing cells. The small deletions were ascertained by locus specific probes for13q14 (Rb gene), 17p13 (p53 protein) and 11q23 (MLL gene). These genes are responsible for cell division and theirfunction is probably in connection with neoplastic process. It is of interest whether numerical and structuralchromosomal rearrangements are primary or secondary changes and what is their impact on etiology of CLL.93 patients were examined by DNA prove CEP12 and trisomy 12 was found in 24 of them (25.8 %), the range ofthe clone was 2.5-75.5 % of the screened cells. Deletion del(13)(q14) was examined by probe D13S319 in 73 patientsand proved in 24 of them (32.8 %), pathological clone ranged 2.5-80.0 % of the cells. Deletion del(17)(p13) wasfound in 14 patients out of 61 examined by probe LSI p53 (22.9 %). The extent of the clone was 2.5-34.0 % ofexamined cells. Deletion 11q23 was not ascertained in any of 11 patients by means of probe LSI 11q23 (MLL). Allprobes used for FISH were manufactured by VYSIS™.Conclusions. FISH is very sensitive method, suitable for molecular-cytogenetic examination of leukemic patients.With I-FISH the deletion of 13q14 was ascertained as the most frequent chromosomal aberration in series of73 patients with CLL. We continue to increase the number of patients screened by I-FISH with all eligible DNAprobes and start the prospective study on patients with chromosomal pathology. We will correlate the immunophe-notype, morphology, clinical course and prognosis with karyotypic findings.

Key words:
CLL, I-FISH, trisomy 12, deletion 13q, deletion 17p, deletion 11q.

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