In vitro sensitivity to dasatinib in lymphoblasts from a patient with t(17;19)(q22;p13) gene rearrangement pre-B acute lymphoblastic leukemia

Patients with t(17;19) acute lymphoblastic leukemia (ALL) have a dismal prognosis even with the most intensive current therapies that include stem cell transplant. We present the case of a patient with t(17;19)(q22;p13) gene rearranged B‐cell precursor ALL whose lymphoblasts were found to have significant in vitro sensitivity to dasatinib. The patient tolerated the addition of dasatinib with combination therapy and remained in remission for over nine months until his recurrence. Therefore, future studies will be needed to interrogate whether dasatinib has any therapeutic benefit in children with t(17;19) B‐cell precursor ALL. Pediatr Blood Cancer 2012;59:576–579. © 2011 Wiley Periodicals, Inc.

[1]  H. Kantarjian,et al.  First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. , 2010, Blood.

[2]  N. Heerema,et al.  Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  M. Hallek,et al.  The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic leukemia cells in vitro with preference for a subgroup of patients with unmutated IgVH genes. , 2008, Blood.

[4]  T. Chiles,et al.  Sensitive to Rottlerin, and Depends on Lyn Parallel with the Classical Pathway, Is Pathway for BCR Signaling Operates in Cross-Talk: The IL-4-Induced Alternate Cutting Edge: B Cell Receptor (BCR) , 2007 .

[5]  T. Inaba,et al.  Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19 , 2007, Leukemia.

[6]  M. Baudis,et al.  ABCB1 over‐expression and drug‐efflux in acute lymphoblastic leukemia cell lines with t(17;19) and E2A‐HLF expression , 2006, Pediatric blood & cancer.

[7]  S. Bailey,et al.  Characterization of the t(17;19) translocation by gene-specific fluorescent in situ hybridization-based cytogenetics and detection of the E2A-HLF fusion transcript and protein in patients' cells. , 2006, Haematologica.

[8]  D. Fabbro,et al.  Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia , 2004, Nature Genetics.

[9]  J. Downing,et al.  The E2A-HLF Oncoprotein ActivatesGroucho-Related Genes and SuppressesRunx1 , 2001, Molecular and Cellular Biology.

[10]  J. Kersey.  Fifty years of studies of the biology and therapy of childhood leukemia. , 1997, Blood.

[11]  S. Hunger,et al.  Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. , 1996, Blood.

[12]  M. Cleary,et al.  Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. , 1992, Genes & development.

[13]  F. Behm,et al.  New recurring chromosomal translocations in childhood acute lymphoblastic leukemia. , 1991, Blood.

[14]  J. E. Carceller.  American Society of Pediatric Hematology/Oncology: , 1990 .