Similar Patterns of Chromosome Abnormalities in CML Occur in Addition to the Philadelphia Translocation with or without Tyrosine Kinase Inhibitor Treatment.
Authors: Haferlach Claudia , Bacher Ulrike , Schnittger Susanne , Weiss Tamara , Kern Wolfgang , Haferlach Torsten 
Published: October 2019

Abstract 3270

Poster Board III-1

In chronic myeloid leukemia (CML), the progress from chronic phase (CP) to accelerated (AP)/blast phase (BP) is frequently accompanied by cytogenetic evolution within the Philadelphia (Ph+) positive clone. It was shown that additional chromosomal alterations follow non-random patterns with frequent occurrence of “major route” (e.g. +Ph, i(17q), +8) and “minor route” changes (e.g. -Y, -7 or +21). Corresponding to the pre-imatinib era, Ph+ clonal cytogenetic evolution was still identified to worsen prognosis in patients receiving imatinib. However, whether the introduction of TKIs changed the pattern of additional chromosome aberrations, was not studied so far. We here compared two subgroups: 1.) 245 CML patients treated with tyrosine kinase inhibitors (TKIs) with clonal evolution in the Ph+ clone investigated in the Munich Leukemia Laboratory (MLL) between 2005–2009. 2.) 500 CML cases published in the Mitelman Database (http://cgap.nci.nih.gov/Chromosomes/Mitelman) before the year 2000 (i.e. before the introduction of imatinib into the treatment of CML). The 245 patients from our cohort were selected for this study based on the occurrence of Ph+ clonal evolution at diagnosis or during the course of CML. Patients received imatinib or 2nd generation TKIs. First, analysis was performed for the Mitelman cohort and for the MLL cohort. Then, analysis was separated for those patients from the MLL cohort who showed Ph+ clonal evolution already at diagnosis of CML before start of TKIs (n=91), and for those patients who developed Ph+ cytogenetic alterations during TKIs (n=154). The patterns of chromosomal gains and losses were analyzed with the support of the CyDAS cytogenetic data analysis system (http://www.cydas.org/OnlineAnalysis/). All 4 cohorts showed comparable patterns of chromosomal gains/losses in addition to the Philadelphia translocation: Most frequent were +8, +Ph chromosome, +19, and i(17)(q10), and -Y. Less frequent were -7 and +21. Therefore, no difference between the patterns of abnormalities dating from the pre-imatinib era (data from the Mitelman database) or after the introduction of TKI (MLL cohort) was obvious. Also, there was no difference in cytogenetic patterns between patients who showed Ph+ clonal evolution at diagnosis of CML already and those who acquired them during TKI treatment. In conclusion, the patterns of cytogenetic alterations in the Ph+ clones in CML are similar as investigated in the pre-TKI and the TKI eras and therefore are independent, i.e. of the time point of analysis at diagnosis or during follow-up and also treatment of CML.

Disclosures:

Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Weiss:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.