|
|
Prepublished online as a Blood First Edition Paper on March 27, 2003; DOI 10.1182/blood-2002-06-1756.
Submitted June 13, 2002
Accepted March 13, 2003
Presence of the BCR-ABL mutation E255K prior to STI571 (Imatinib) treatment in patients with Ph+ acute lymphoblastic leukemia
Wolf-Karsten Hofmann*, Martina Komor, Barbara Wassmann, Letetia C Jones, Harald Gschaidmeier, Dieter Hoelzer, H Phillip Koeffler, and Oliver G Ottmann
Department of Hematology, University Hospital, Frankfurt/Main, Germany
Division of Hematology/Oncology, Cedars Sinai Research Institute, UCLA School of Medicine, Los Angeles, CA, USA
Novartis Pharma AG, Nuremberg, Germany
* Corresponding author; email: W.K.Hofmann{at}em.uni-frankfurt.de.
The tyrosine kinase inhibitor STI571 (Imatinib) binds competitively to the ATP binding site of the ABL kinase, thereby inhibiting auto- and substrate phosphorylation of the oncogenic protein BCR-ABL and preventing the activation of downstream signaling pathways. Comparative studies on leukemic cell samples obtained from CML and Ph+ ALL patients before and after treatment with STI571 reported point mutations in resistant samples after a short time of therapy. The aim of this study was to determine whether or not patients with Ph+ ALL in whom resistance developed as a consequence of the E255K mutation already harboured this subclone prior to STI571 treatment. First, the migration pattern of cDNA's from 30 bone marrow samples from patients with Ph+ ALL was analyzed by PCR-SSCP. Thereafter, detailed mutational analysis using genomic DNA was performed on initial STI571 naive bone marrow samples of 4 individuals with Ph+ ALL, for whom the mutation E255K in association with STI571-treatment had been shown. A 166 bp PCR-fragment spanning from nt 862 to nt 1027 was cloned and 108 clones per sample were analyzed by direct sequencing. This more sensitive technique revealed presence of the E255K mutation in 2 initial samples, one clone each. We identified for the first time the mutation E255K in STI571-naive leukemic samples of Ph+ ALL-patients. The findings suggest that the mutation exists in a very small sub-population of leukemic cells at the beginning of STI571 therapy.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Pfeifer, B. Wassmann, A. Pavlova, L. Wunderle, J. Oldenburg, A. Binckebanck, T. Lange, A. Hochhaus, S. Wystub, P. Bruck, et al.
Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)
Blood,
July 15, 2007;
110(2):
727 - 734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Vignetti, P. Fazi, G. Cimino, G. Martinelli, F. Di Raimondo, F. Ferrara, G. Meloni, A. Ambrosetti, G. Quarta, L. Pagano, et al.
Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol
Blood,
May 1, 2007;
109(9):
3676 - 3678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Skaggs, M. E. Gorre, A. Ryvkin, M. R. Burgess, Y. Xie, Y. Han, E. Komisopoulou, L. M. Brown, J. A. Loo, E. M. Landaw, et al.
Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants
PNAS,
December 19, 2006;
103(51):
19466 - 19471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kosaka, Y. Yatabe, H. Endoh, K. Yoshida, T. Hida, M. Tsuboi, H. Tada, H. Kuwano, and T. Mitsudomi
Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib.
Clin. Cancer Res.,
October 1, 2006;
12(19):
5764 - 5769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Koyama, S. Koschmieder, S. Tyagi, I. Portero-Robles, J. Chromic, S. Myloch, H. Nurnberger, T. Rossmanith, W.-K. Hofmann, D. Hoelzer, et al.
Inhibition of phosphotyrosine phosphatase 1B causes resistance in BCR-ABL-positive leukemia cells to the ABL kinase inhibitor STI571.
Clin. Cancer Res.,
April 1, 2006;
12(7 Pt 1):
2025 - 2031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Willis, T. Lange, S. Demehri, S. Otto, L. Crossman, D. Niederwieser, E. P. Stoffregen, S. McWeeney, I. Kovacs, B. Park, et al.
High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy
Blood,
September 15, 2005;
106(6):
2128 - 2137.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Wassmann, H. Pfeifer, M. Stadler, M. Bornhauser, G. Bug, U. J. Scheuring, P. Bruck, M. Stelljes, R. Schwerdtfeger, N. Basara, et al.
Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)
Blood,
July 15, 2005;
106(2):
458 - 463.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Soverini, G. Martinelli, G. Rosti, S. Bassi, M. Amabile, A. Poerio, B. Giannini, E. Trabacchi, F. Castagnetti, N. Testoni, et al.
ABL Mutations in Late Chronic Phase Chronic Myeloid Leukemia Patients With Up-Front Cytogenetic Resistance to Imatinib Are Associated With a Greater Likelihood of Progression to Blast Crisis and Shorter Survival: A Study by the GIMEMA Working Party on Chronic Myeloid Leukemia
J. Clin. Oncol.,
June 20, 2005;
23(18):
4100 - 4109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Lee, Y.-J. Kim, C.-K. Min, H.-J. Kim, K.-S. Eom, D.-W. Kim, J.-W. Lee, W.-S. Min, and C.-C. Kim
The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia
Blood,
May 1, 2005;
105(9):
3449 - 3457.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Bagrintseva, S. Geisenhof, R. Kern, S. Eichenlaub, C. Reindl, J. W. Ellwart, W. Hiddemann, and K. Spiekermann
FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L)
Blood,
May 1, 2005;
105(9):
3679 - 3685.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. von Bubnoff, D. R. Veach, H. van der Kuip, W. E. Aulitzky, J. Sanger, P. Seipel, W. G. Bornmann, C. Peschel, B. Clarkson, and J. Duyster
A cell-based screen for resistance of Bcr-Abl-positive leukemia identifies the mutation pattern for PD166326, an alternative Abl kinase inhibitor
Blood,
February 15, 2005;
105(4):
1652 - 1659.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. G. Ottmann and B. Wassmann
Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Hematology,
January 1, 2005;
2005(1):
118 - 122.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A.E. Irving, S. O'Brien, A. L. Lennard, L. Minto, F. Lin, and A. G. Hall
Use of Denaturing HPLC for Detection of Mutations in the BCR-ABL Kinase Domain in Patients Resistant to Imatinib
Clin. Chem.,
July 1, 2004;
50(7):
1233 - 1237.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Soverini, G. Martinelli, M. Amabile, A. Poerio, M. Bianchini, G. Rosti, F. Pane, G. Saglio, and M. Baccarani
Denaturing-HPLC-Based Assay for Detection of ABL Mutations in Chronic Myeloid Leukemia Patients Resistant to Imatinib
Clin. Chem.,
July 1, 2004;
50(7):
1205 - 1213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Thomas, S. Faderl, J. Cortes, S. O'Brien, F. J. Giles, S. M. Kornblau, G. Garcia-Manero, M. J. Keating, M. Andreeff, S. Jeha, et al.
Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate
Blood,
June 15, 2004;
103(12):
4396 - 4407.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-H. Liu, M. Kaur, G. Wang, P. Zhu, Y. Zhang, and G. M. Makrigiorgos
Inverse PCR-Based RFLP Scanning Identifies Low-Level Mutation Signatures in Colon Cells and Tumors
Cancer Res.,
April 1, 2004;
64(7):
2544 - 2551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
