High levels of BAX, low levels of MRP-1, and high platelets are independent predictors of response to imatinib in myeloid blast crisis of CML.
Imatinib induces remissions in approximately 30% of patients with chronic myeloid leukemia (CML) in myeloid blast crisis (M-BC). Because most patients eventually relapse, allogeneic stem cell transplantation (SCT) in remission offers the best chance for cure. Remission induction with imatinib alone would seem ideal because it is less toxic than conventional chemotherapy. Conversely, patients unlikely to respond may benefit from combination therapy up front. To identify prognostic factors, we studied the mRNA expression of genes related to drug resistance and apoptosis in leukemic cells from patients with M-BC and their in vitro sensitivity to imatinib, and analyzed the results with other baseline factors for their impact on response. We show that high levels of BAX, low levels of MRP-1, and a high platelet count are independently predictive of response to imatinib. Combined into a score, these parameters may be clinically useful for risk-adapted patient stratification.
Lange
Thoralf
T
Department of Hematology, University of Leipzig, Germany.
Günther
Christine
C
Köhler
Thomas
T
Krahl
Rainer
R
Musiol
Scarlet
S
Leiblein
Sabine
S
Al-Ali
Haifa-Kathrin
HK
van Hoomissen
Iris
I
Niederwieser
Dietger
D
Deininger
Michael W N
MW
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy; D019742:Chemokines, CC / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D010976:Platelet Count; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D012074:Remission Induction; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
D018952:Antigens, CD34; D000970:Antineoplastic Agents; C494826:BAX protein, human; D001549:Benzamides; D019742:Chemokines, CC; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C070959:Ccl6 protein, mouse; D000068877:Imatinib Mesylate