The incidence of atypical patterns ofBCR-ABL1rearrangement and molecular-cytogenetic response to tyrosine kinase inhibitor therapy in newly diagnosed cases with chronic myeloid leukemia (CML)

Abstract

BackgroundTo analyze the frequency of atypical fluorescence in situ hybridization signal patterns and estimate the complete cytogenetic response (CCyR) and major molecular response (MMR) during 12 months of tyrosine kinase inhibitor therapy in patients with newly diagnosed chronic myeloid leukemia.MethodsThe study included bone marrow and peripheral blood samples from 122 patients with newly diagnosed chronic myeloid leukemia. Detection of the breakpoint cluster region—Abelson fusion gene (BCR-ABL1) was performed using fluorescence in situ hybridization with a dual-color dual-fusion translocation probe, and MMR analysis was performed using the real-time quantitative polymerase chain reaction method.ResultsVariant translocation was determined in 10 samples and a deletion on the derivative chromosome 9 (del/der(9)) was found in 20 samples. The rates of CCyR and MMR were similar between patients with reciprocal translocation, variant translocation, deletion of derivative BCR, or ABL1-BCR fusion gene. The Kaplan-Meier test did not show any significant differences in the rates of CCyR and MMR among those groups of patients.ConclusionThe frequencies of variant translocation and del/der(9) in the present study agree with the results of other studies performed worldwide. No differences were observed in the rates of CCyR and MMR between patients with atypical patterns and reciprocal translocation.

Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): An Update

“…Their findings suggest that CML patients in the accelerated phase or in blast crisis (AP/BC) with der(9) deletions show poor response to IM therapy. However, for CML patients in the chronic phase (CP), deletion of ABL1-BCR did not result in poor response to imatinib or lower rates of either complete cytogenetic or major molecular responses (Quintas-Cardama et al, 2011;Svabek et al, 2018). While it suggested that clonal copy number aberrations remain a hallmark of disease progression (Shao et al, 2015), the mechanism of the disease progression has not been fully illustrated.…”

Genomic Mechanisms Influencing Outcome in Chronic Myeloid Leukemia

“…Derivative 9 deletions are also detectable by FISH analysis. The figure represents an ABL1 deletion of an interphase nucleus derived from Figure 2D from Švabek et al [107]. These are below the size resolution for detection using chromosome banding.…”