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

Thoralf Lange; Christine Günther; Thomas Köhler; Rainer Krahl; Scarlet Musiol; Sabine Leiblein; Haifa-Kathrin Al-Ali; Iris van Hoomissen; Dietger Niederwieser; Michael W N Deininger

doi:10.1182/blood-2002-05-1366

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

Blood. 2003 Mar 15;101(6):2152-5. doi: 10.1182/blood-2002-05-1366. Epub 2002 Oct 24.

Authors

Thoralf Lange¹, Christine Günther, Thomas Köhler, Rainer Krahl, Scarlet Musiol, Sabine Leiblein, Haifa-Kathrin Al-Ali, Iris van Hoomissen, Dietger Niederwieser, Michael W N Deininger

Affiliation

¹ Department of Hematology, University of Leipzig, Germany.

PMID: 12406906
DOI: 10.1182/blood-2002-05-1366

Abstract

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.

Publication types

Clinical Trial
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antigens, CD34 / analysis
Antineoplastic Agents / therapeutic use*
Apoptosis / genetics
Benzamides
Blast Crisis / drug therapy
Chemokines, CC / genetics*
Drug Resistance, Neoplasm / genetics
Drug Screening Assays, Antitumor
Female
Gene Expression
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
Male
Middle Aged
Piperazines / therapeutic use*
Platelet Count*
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins c-bcl-2*
Pyrimidines / therapeutic use*
RNA, Messenger / analysis
Remission Induction
Stem Cell Transplantation
Transplantation, Homologous
Tumor Cells, Cultured
bcl-2-Associated X Protein

Substances

Antigens, CD34
Antineoplastic Agents
BAX protein, human
Benzamides
Chemokines, CC
Piperazines
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
Pyrimidines
RNA, Messenger
bcl-2-Associated X Protein
Ccl6 protein, mouse
Imatinib Mesylate