Sustained complete hematologic remission after administration of the tyrosine kinase inhibitor imatinib mesylate in a patient with refractory, secondary AML.

Imatinib mesylate, a tyrosine kinase inhibitor targeting bcr-abl, platelet-derived growth factor receptor (PDGF-R), and c-Kit, effectively induces hematologic and cytogenetic remissions in bcr-abl(+) chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) with only mild to moderate side effects. Here, we describe the successful treatment of a 64-year-old man with c-Kit(+) secondary acute myeloid leukemia (AML) refractory to standard chemotherapy. Upon 2 weeks of imatinib mesylate administration, the patient achieved a complete hematologic remission in peripheral blood. In addition, complete clearance of leukemic blasts in bone marrow and a significant cytogenetic response lasting for more than 5 months was observed. Sequence analysis of exons 2, 8, 10, 11, and 17 of the c-Kit receptor did not reveal structural alterations as previously described in a subset of AML cases. This is the first report of complete remission achieved upon administration of imatinib mesylate in a patient with highly refractory, secondary AML.

[1]  M. Baccarani,et al.  Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. , 2002, The New England journal of medicine.

[2]  Ø. Bruserud,et al.  Platelet‐derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blasts , 2001, European journal of haematology.

[3]  Y. Ma,et al.  Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy. , 2001, Leukemia research.

[4]  D. Tuveson,et al.  Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. , 2001, The New England journal of medicine.

[5]  J. Cherrington,et al.  The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts. , 2001, Blood.

[6]  B. Druker,et al.  Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. , 2000, The Journal of pharmacology and experimental therapeutics.

[7]  C. L. Perkins,et al.  CGP57148B (STI-571) induces differentiation and apoptosis and sensitizes Bcr-Abl-positive human leukemia cells to apoptosis due to antileukemic drugs. , 2000, Blood.

[8]  B. Druker,et al.  Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. , 2000, Blood.

[9]  D. Linnekin,et al.  Early signaling pathways activated by c-Kit in hematopoietic cells. , 1999, The international journal of biochemistry & cell biology.

[10]  J. Reilly,et al.  c‐kit proto‐oncogene exon 8 in‐frame deletion plus insertion mutations in acute myeloid leukaemia , 1999, British journal of haematology.

[11]  D. Heitjan,et al.  Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Hirota,et al.  Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. , 1998, Science.

[13]  Jürg Zimmermann,et al.  Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells , 1996, Nature Medicine.

[14]  John Malysz,et al.  W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity , 1995, Nature.

[15]  W. Gerald,et al.  Expression of c-kit and kit ligand proteins in normal human tissues. , 1994, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[16]  H. Kitayama,et al.  Expression, function and activation of the proto-oncogene c-kit product in human leukemia cells. , 1993, Leukemia & lymphoma.

[17]  I. Bernstein,et al.  Blasts from patients with acute myelogenous leukemia express functional receptors for stem cell factor. , 1992, Blood.

[18]  R. Spritz,et al.  Dominant negative and loss of function mutations of the c-kit (mast/stem cell growth factor receptor) proto-oncogene in human piebaldism. , 1992, American journal of human genetics.

[19]  H. Kitayama,et al.  Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells. , 1991, Blood.

[20]  T Takahashi,et al.  Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer. , 1991, Oncogene.

[21]  C. Brannan,et al.  Requirement for mast cell growth factor for primordial germ cell survival in culture , 1991, Nature.

[22]  S. Nishikawa,et al.  Expression and function of c-kit in hemopoietic progenitor cells , 1991, The Journal of experimental medicine.

[23]  L. Larizza,et al.  Amplification of a novel c-Kit activating mutation Asn(822)-Lys in the Kasumi-1 cell line: a t(8;21)-Kit mutant model for acute myeloid leukemia. , 2002, The hematology journal : the official journal of the European Haematology Association.

[24]  J. Smith,et al.  C-kit mutation screening in patients with acute myeloid leukaemia: adaptation of a Giemsa-stained bone-marrow smear DNA extraction technique. , 2001, British journal of biomedical science.