New genetic abnormalities and treatment response in acute lymphoblastic leukemia.

Numerous genetic abnormalities have been identified in acute lymphoblastic leukemia (ALL). Here we review the recurrent abnormalities with emphasis on those recently discovered, and discuss their association with chemotherapy resistance or sensitivity and with clinical response to therapy. Also, the role of genetic abnormalities in leukemogenesis and their potential as therapeutic targets will be discussed.

[1]  W. Evans,et al.  Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells. , 2009, Blood.

[2]  R. Pieters,et al.  Molecular‐genetic insights in paediatric T‐cell acute lymphoblastic leukaemia , 2008, British journal of haematology.

[3]  A. Hall,et al.  Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia. , 2008, Cancer research.

[4]  S. Mustjoki,et al.  Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. , 2008, Blood.

[5]  A. Ferrando,et al.  NOTCH1 extracellular juxtamembrane expansion mutations in T-ALL. , 2008, Blood.

[6]  J. Downing,et al.  Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL. , 2008, Genes & development.

[7]  E. Thiel,et al.  Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group , 2008, Leukemia.

[8]  Christopher B. Miller,et al.  BCR–ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros , 2008, Nature.

[9]  A. Ferrando,et al.  The role of the PTEN/AKT Pathway in NOTCH1-induced leukemia , 2008, Cell cycle.

[10]  R. Pieters,et al.  Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. , 2008, Blood.

[11]  B. Johansson,et al.  FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns , 2008, Genes, chromosomes & cancer.

[12]  B. Johansson,et al.  Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia , 2008, Genes, chromosomes & cancer.

[13]  Christian Urban,et al.  Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. , 2007, Blood.

[14]  Andrew P. Stubbs,et al.  The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia. , 2007, Blood.

[15]  R. Stam,et al.  Prognostic significance of high-level FLT3 expression in MLL-rearranged infant acute lymphoblastic leukemia. , 2007, Blood.

[16]  F. Sigaux,et al.  p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis. , 2007, Blood.

[17]  Rob Pieters,et al.  FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to γ-secretase inhibitors , 2007, The Journal of experimental medicine.

[18]  A. Ferrando,et al.  The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia , 2007, The Journal of experimental medicine.

[19]  R. Pieters,et al.  A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial , 2007, The Lancet.

[20]  U. Lendahl,et al.  The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling. , 2007, Cancer research.

[21]  R. Pieters,et al.  Microarray-based identification of new targets for specific therapies in pediatric leukemia. , 2007, Current Drug Targets.

[22]  M. Busslinger,et al.  Pax5: the guardian of B cell identity and function , 2007, Nature Immunology.

[23]  J. Hehir-Kwa,et al.  High-resolution genomic profiling of childhood ALL reveals novel recurrent genetic lesions affecting pathways involved in lymphocyte differentiation and cell cycle progression , 2007, Leukemia.

[24]  Christopher B. Miller,et al.  Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia , 2007, Nature.

[25]  S. Richards,et al.  Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21). , 2007, Blood.

[26]  J. Aster,et al.  The multifaceted role of Notch in cancer. , 2007, Current opinion in genetics & development.

[27]  Yi Zhang,et al.  Leukaemic transformation by CALM–AF10 involves upregulation of Hoxa5 by hDOT1L , 2006, Nature Cell Biology.

[28]  M. Muckenthaler,et al.  Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. , 2006, Blood.

[29]  J. Aster,et al.  A phase I clinical trial of the notch inhibitor MK-0752 in patients with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and other leukemias. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  M. Bhasin,et al.  p16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice , 2006, Oncogene.

[31]  R. Pieters,et al.  Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and COALL-treated t(12;21)-positive pediatric ALL, and their relation with drug sensitivity and clinical outcome , 2006, Leukemia.

[32]  C. Pui,et al.  Treatment of acute lymphoblastic leukemia. , 2006, The New England journal of medicine.

[33]  R. Stam,et al.  Activating FLT3 mutations in CD4+/CD8- pediatric T-cell acute lymphoblastic leukemias. , 2005, Blood.

[34]  E. Macintyre,et al.  CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes , 2005, Leukemia.

[35]  S. Armstrong,et al.  Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia. , 2005, Blood.

[36]  M. D. Boer,et al.  CDKN2 deletions have no prognostic value in childhood precursor-B acute lymphoblastic leukaemia , 2005, Leukemia.

[37]  F. Sigaux,et al.  HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL). , 2005, Blood.

[38]  Yi Zhang,et al.  hDOT1L Links Histone Methylation to Leukemogenesis , 2005, Cell.

[39]  M. Relling,et al.  Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia. , 2005, Cancer cell.

[40]  P. Marynen,et al.  A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias , 2005, Leukemia.

[41]  Dario Campana,et al.  FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression. , 2005, Blood.

[42]  M. Bernstein,et al.  Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: results from a Children's Oncology Group phase 1 study. , 2004, Blood.

[43]  Andrew P. Weng,et al.  Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia , 2004, Science.

[44]  A. Ferrando,et al.  Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia , 2004, Nature Genetics.

[45]  Cheng Cheng,et al.  Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. , 2004, The New England journal of medicine.

[46]  S. Armstrong,et al.  FLT3 mutations in childhood acute lymphoblastic leukemia. , 2004, Blood.

[47]  M. Caligiuri,et al.  Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia , 2004, The Lancet.

[48]  W. Kern,et al.  Satelite Symposium V, Meet-the-Professor Sessions I and II, Main Sessions I-IX , 2004, Annals of Hematology.

[49]  F. Speleman,et al.  Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951. , 2004, Blood.

[50]  E. Macintyre,et al.  CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRγδ lineage , 2003 .

[51]  S. Armstrong,et al.  Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation. , 2003, Blood.

[52]  Rob Pieters,et al.  Inhibition of FLT3 in MLL. Validation of a therapeutic target identified by gene expression based classification. , 2003, Cancer cell.

[53]  R. Pieters,et al.  In vitro drug resistance profile of Philadelphia positive acute lymphoblastic leukemia is heterogeneous and related to age: a report of the Dutch and German Leukemia Study Groups. , 2002, Medical and pediatric oncology.

[54]  E. Lander,et al.  Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. , 2002, Cancer cell.

[55]  R. Pieters,et al.  TEL/AML1 gene fusion is related to in vitro drug sensitivity for L-asparaginase in childhood acute lymphoblastic leukemia. , 2000, Blood.

[56]  T. Hoang,et al.  SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-Tα chain expression , 2000, Nature Immunology.

[57]  O. Eden,et al.  Monosomy 20 as a pointer to dicentric (9;20) in acute lymphoblastic leukemia , 2000, Leukemia.

[58]  Wan Ariffin Bin Abdullah,et al.  Med Pediatr Oncol , 1999 .

[59]  Y. Hayashi,et al.  Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia. , 1999, Leukemia research.

[60]  M. D. Boer,et al.  Relation between age, immunophenotype and in vitro drug resistance in 395 children with acute lymphoblastic leukemia–implications for treatment of infants , 1998, Leukemia.

[61]  M. Link,et al.  Frequent and selective methylation of p15 and deletion of both p15 and p16 in T-cell acute lymphoblastic leukemia. , 1997, Cancer research.

[62]  R. Pieters,et al.  Favorable prognosis of hyperdiploid common acute lymphoblastic leukemia may be explained by sensitivity to antimetabolites and other drugs: results of an in vitro study. , 1995, Blood.

[63]  J. Sklar,et al.  Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia , 1991, The Journal of experimental medicine.

[64]  J. Sklar,et al.  TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms , 1991, Cell.

[65]  J. Meijerink,et al.  Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences , 2008, Leukemia.

[66]  A. Rolink,et al.  PAX5/TEL acts as a transcriptional repressor causing down-modulation of CD19, enhances migration to CXCL12, and confers survival advantage in pre-BI cells. , 2008, Cancer research.

[67]  W. Kamps,et al.  The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols. , 2006, Haematologica.

[68]  P. Marynen,et al.  Genetic insights in the pathogenesis of T-cell acute lymphoblastic leukemia. , 2005, Haematologica.

[69]  W. Tissing,et al.  Molecular determinants of glucocorticoid sensitivity and resistance in acute lymphoblastic leukemia , 2003, Leukemia.