Molecular monitoring and mutation analysis of patients with advanced phase CML and Ph+ ALL receiving dasatinib

• Published in: European journal of haematology 2010-11, Vol.85 (5), p.399-404
• Main Authors: Olsson-Strömberg, Ulla, Hermansson, Monica, Lundán, Tuija, Ohm, Anne-Charlotte, Engdahl, Ida, Höglund, Martin, Simonsson, Bengt, Porkka, Kimmo, Barbany, Gisela
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; chronic myeloid leukemia; Clone Cells - pathology; Dasatinib; DNA Mutational Analysis; Female; Fusion Proteins, bcr-abl - genetics; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myeloid, Accelerated Phase - drug therapy; Leukemia, Myeloid, Accelerated Phase - genetics; Male; Medicin och hälsovetenskap; Middle Aged; molecular monitoring; mutation; Polymerase Chain Reaction - methods; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Pyrimidines - therapeutic use; RNA, Neoplasm - genetics; Thiazoles - therapeutic use; Young Adult
• ISSN: 0902-4441; 1600-0609; 1600-0609
• DOI: 10.1111/j.1600-0609.2010.01506.x

As a result of the excellent responses achieved in chronic phase chronic myeloid leukemia since the introduction of imatinib, sensitive techniques such as reverse transcriptase real‐time PCR are warranted to monitor patients receiving tyrosine kinase inhibitors (TKI). Our objective was to determine the value of molecular monitoring Ph‐positive leukemias under dasatinib treatment. We used real‐time PCR and ABL1 kinase domain sequencing on sequential samples from 11 patients with Philadelphia‐positive leukemias who received dasatinib. We were able to detect pre‐existing mutations in the kinase domain of BCR‐ABL1 in four patients, particularly in patients with high BCR‐ABL1 transcript levels. Most mutations disappeared with dasatinib, however, in five patients a clone with T315I appeared during dasatinib treatment. We conclude that sensitive molecular monitoring with real‐time PCR for BCR‐ABL1 transcripts and mutation screening of the ABL1 kinase domain of patients with Philadelphia‐positive leukemias are valuable for patient management, however, mutation findings should be interpreted with caution, as mutant clones not always behave in vivo as predicted by in vitro assays.