Diagnosis and Disease Management in CML Patients Using Conventional and Molecular Cytogenetics

Document Type: Research Paper


1 Division of Genetics, Department of Anatomy, All India Institute of Medical Sciences,New Delhi

2 Division of Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi


Chronic Myeloid Leukemia (CML) is a hematopoietic malignancy characterized by the presence of
Philadelphia (Ph1) chromosome that results from balanced reciprocal translocation between chromosomes
9 and 22 leading in the formation of bcr/abl fusion gene. The present study was conducted to evaluate cytogenetic and molecular abnormalities in CML patients at presentation and during the course of therapy. Cytogenetic analysis was carried out in bone marrow samples of 165 suspected patients of CML using standard protocols. Sequential cytogenetic analysis was also done in 55 CML patients (50 on IFN-α 2b therapy and 5 on Hydroxyurea) up to variable period of 3 years. Fluorescence In Situ Hybridization (FISH) using specific probes for bcr and abl genes was carried out in cases where conventional cytogenetics was not informative, in cases that were Ph-negative at presentation and in cases with complete or major cytogenetic response (<34%
Ph+cells). Of the 165 CML patients, 157 patients (95%) were Ph-positive while 8 patients (5%) were
Ph-negative. Cytogenetic abnormalities other than the standard Ph1 translocation were observed in 2
Ph+ patients and 2 Ph-negative patients. Sequential cytogenetic analysis revealed varied degrees of cytogenetic response in 35 patients on IFN-α 2b therapy.
Complete cytogenetic response was observed in 8 patients (16%) on IFN-α 2b therapy. However, FISH
analysis could detect bcr/abl fusion gene in some of these cases. This finding highlights the sensitivity of
this technique in detecting residual disease even in patients with complete cytogenetic remission. The
other patients in complete cytogenetic remission did not have evidence of bcr/abl fusion. FISH analysis
also revealed bcr/abl fusion signals in Ph-negative cases (with no cytogenetic abnormality) indicating a
masked translocation or a sub-microscopic rearrangement.
Thus, the results of the present study show that analysis of cancer patients on therapy at the molecular
level has tremendous importance for management of CML patients. Further, with the use of highly sensitive FISH technique, results can be obtained within 24 hours thereby, aiding rapid diagnosis and management of these patients. This efficient and highly sensitive molecular cytogenetic technique can also be done on interphase cells and poorly spread metaphases thereby, overcoming the difficulty of conventional chromosomal analysis especially in patients on therapy.