Cytogenetic Clonal Evolution in Patients with Chronic Myeloid Leukemia

ABSTRACT

Chronic myeloid leukaemia (CML) is a clonal haematological disease characterised by t(9;22)(q34;q11) which is called Philadelphia (Ph) chromosome. Highly improved haematological and cytogenetic results were obtained in chronic phase CML with the introduction of imatinib. Occurrence of additional cytogenetic abnormalities in Ph(+) cells is defined as clonal evolution (CE) and considered to be a preceding sign for acceleration. The most common additional chromosomal changes are +8, +Ph, i(17q), +19, -Y, +21, +17 and-7. The aims of this study were to delineate the occurrence pattern of cytogenetic clonal evolution in our cohort of CML patients and to investigate the impact on the course and prognosis of CML. Additional clonal chromosomal changes in Ph(+) cells were observed in 20 cases (19%). The abnormalities seen were monosomy 21 (%35), -17 (%30), -19 and +8 in (%25), -7, -8, -13, -15, -22, +Ph, and different marker chromosomes (%20), -Y, -12, -14, -16, -20 (%15), +Y, -10, -18 (%10), and -X, -3, -9, +20, der(7;17)(q10;q10), der3?, der12? (%5). The findings of-Y, -7, -8, +8, -14, -15, -17, -18, -21, +Ph, der(7;17)(q10;q10) and del(7)(q11) have been recorded in more than one samples in at least one case. The clinical data of the 20 cases with CE were compared to 7 cases with no or minor cytogenetic response without CE and no statistically significant differences found. Considering their high frequency and persistence in successive samples, we recommend to trace -21 and -17 with FISH in addition to classical cytogenetics in CML cases.

Keywords:

• CML
• Cytogenetics
• Clonal evolution
• imatinib