FISH for BCR-ABL on interphases of peripheral blood neutrophils but not of unselected white cells correlates with bone marrow cytogenetics in CML patients treated with imatinib

Abstract

Interphase fluorescence in situ hybridization (I-FISH) for the BCR-ABL translocation performed on peripheral blood (PB) white cells has been suggested as a surrogate for conventional bone marrow (BM) cytogenetics for monitoring patients with chronic myeloid leukemia (CML). I-FISH is faster, less costly, and does not require BM aspiration. For patients treated with interferon-alpha (IFN), a good correlation between the two methods has been demonstrated in several though not all studies. However, imatinib mesylate (STI571) has largely replaced IFN as the standard drug treatment for CML, raising the question if the results obtained in IFN-treated patients are applicable to patients on imatinib. We therefore compared the two methods in patients on imatinib and patients on other therapies, mainly IFN (collectively referred to as nonimatinib therapies). Our results demonstrate that the correlation between I-FISH and cytogenetics is much weaker in patients on imatinib than in patients on nonimatinib therapies. Correction of the I-FISH values for the proportion of lymphocytes barely improved the correlation, probably as a result of unpredictable proportions of Philadelphia-positive B cells. By contrast, I-FISH of PB neutrophils was much better correlated with BM cytogenetics. We conclude that I-FISH on unselected PB white cells is not suitable for monitoring patients on imatinib.

Milestones and Monitoring in Patients with CML Treated with Imatinib

“…11 Nevertheless, one should realize that correlation is not equivalent to concordance and that other studies came to less favorable results, implying that FISH and cytogenetics results may differ significantly in individual patients. 12,13 Another argument against the use of FISH for routine monitoring is that it has never been validated in a clinical trial with real endpoints. Additionally, some commercial labs continue to use old-fashioned probes with a high false-positive rate or fail to indicate their labspecific cutoffs, both of which render the interpretation of the results impossible.…”

Monitoring disease burden in chronic myeloid leukemia: Past, present, and future

“…Interphase FISH assays have the advantage of allowing for testing to be performed on non-dividing cells but are less sensitive than metaphase assays [27], with a false positivity rate as high as 4% due to non-specific background signal depending on the probe used [28,29]. Interphase FISH testing of unselected peripheral blood leukocytes may not correlate with marrow cytogenetic testing [30] as lymphocytes in circulation are not derived from the BCR-ABL1 clone. FISH cannot detect additional chromosomal changes unless they are anticipated and screened with specific probes (i.e., one cannot successfully FISH for trout with a bass lure) [26].…”

Assessment of Interleukin 1β Serum Level in Different Responder Groups and Stages of Chronic Myeloid Leukemia Patients on Imatinb Mesylate Therapy

“…It accounts for 15 % of all adult leukemias [3]. The cytogenetic hallmark of CML is the Philadelphia chromosome (Ph), created by a reciprocal translocation between chromosomes 9 and 22 (t [9; 22] [q34; q11]) [4][5][6].…”