Acute Leukemia : Update of Clinical Aspects

Rearrangements of the MLL gene located at 11q23 are common chromosomal abnormalities associated with acute leukemia (AL), especially infant and secondary leukemia after previous treatment with DNA topoisomerase II inhibitors. 11q23/MLL abnormalities have been widely recognized as an important prognostic factor in AL. Over 70 chromosome partners of 11q23 have been identified to date, at least 50 of which have been cloned and characterized at the molecular level. Recent studies showed that the prognosis of 11q23/MLL AL varies widely according to the partner gene, the leukemia cell lineage, the age of the patient and the treatment administered. Special strategies are needed to treat 11q23/MLL AL, including allogeneic hematopoietic stem cell transplantation, according to the fusion partner. The development of novel methodologies, including new molecular therapeutic targets, is also needed to improve the prognosis of 11q23/MLL AL. The present article provides an update on the current status of prognosis and treatment of 11q23/MLL AL according to the fusion partner.

[1]  R. Marschalek MLL (myeloid/lymphoid or mixed lineage leukemia) , 2011 .

[2]  F. Ciceri,et al.  Allogeneic stem cell transplantation for acute myeloid leukemia , 2010, Haematologica.

[3]  R. Arceci Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study , 2010 .

[4]  富澤 大輔 Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects : a final report of two consecutive studies, MLL96 and MLL98, of the Japan infant leukemia study group , 2010 .

[5]  R. Pieters,et al.  Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. , 2009, Blood.

[6]  S. Raimondi,et al.  Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. , 2009, Blood.

[7]  K. Inokuchi,et al.  The Prognosis and Treatment of Adult Acute Leukemia with 11q23/MLL According to the Fusion Partner , 2009 .

[8]  K. Döhner,et al.  Prognostic factors in adult patients up to 60 years old with acute myeloid leukemia and translocations of chromosome band 11q23: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  M. Liedtke,et al.  Therapeutic targeting of MLL. , 2009, Blood.

[10]  K. Inokuchi,et al.  Treatment of relapsed acute myeloid leukemia with MLL/AF6 fusion after allogeneic hematopoietic stem cell transplantation with gemtuzumab ozogamicin with a long interval followed by donor lymphocyte infusion , 2008, Leukemia.

[11]  K. Oshimi,et al.  Clinical features of adult acute leukemia with 11q23 abnormalities in Japan: a co-operative multicenter study , 2008, International journal of hematology.

[12]  D. Campana,et al.  Age-related differences in leukemia biology and prognosis: the paradigm of MLL-AF4-positive acute lymphoblastic leukemia , 2007, Leukemia.

[13]  S. Armstrong,et al.  Silencing of the tumor suppressor gene FHIT is highly characteristic for MLL gene rearranged infant acute lymphoblastic leukemia , 2006, Leukemia.

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

[15]  A. Borkhardt,et al.  Treatment of relapsed acute myelogeneous leukaemia with MLL/AF6 fusion after stem cell transplantation by intensive reinduction followed by adoptive immunotherapy , 2005, Leukemia.

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

[17]  C. Bloomfield,et al.  Adult de novo acute myeloid leukemia with t(6;11)(q27;q23) , 2004, Cancer.

[18]  C. Bloomfield,et al.  Adult de novo acute myeloid leukemia with t(6;11)(q27;q23): results from Cancer and Leukemia Group B Study 8461 and review of the literature. , 2004, Cancer.

[19]  F. Lo‐Coco,et al.  Chromosomal Aberration of the 11q23 Locus in Acute Leukemia and Frequency of MLL Gene Translocation Results in 378 Adult Patients , 2004 .

[20]  Y. Hayashi,et al.  FLT3 mutations in the activation loop of tyrosine kinase domain are frequently found in infant ALL with MLL rearrangements and pediatric ALL with hyperdiploidy. , 2003, Blood.

[21]  Ching-Hon Pui,et al.  Childhood and adolescent lymphoid and myeloid leukemia. , 2004, Hematology. American Society of Hematology. Education Program.

[22]  W. Hiddemann,et al.  AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. , 2003, Blood.

[23]  J. Radich,et al.  The role of FLT3 in haematopoietic malignancies , 2003, Nature Reviews Cancer.

[24]  C. Pui,et al.  Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements , 2003, Leukemia.

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

[26]  N. Harris,et al.  The World Health Organization (WHO) classification of the myeloid neoplasms. , 2002, Blood.

[27]  S. Fröhling,et al.  Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  C. Pui,et al.  Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region , 2002, The Lancet.

[29]  J. Downing,et al.  Favorable impact of the t(9;11) in childhood acute myeloid leukemia. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  E. Lander,et al.  MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia , 2002, Nature Genetics.

[31]  M. Cleary,et al.  Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins , 2001, Oncogene.

[32]  M. Andersen,et al.  Therapy‐related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on two new cases and review of the literature since 1992 , 2001, British journal of haematology.

[33]  M. Slovak,et al.  Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study , 2000 .

[34]  F. Appelbaum,et al.  Allogeneic stem cell transplantation for relapsed and refractory acute myeloid leukemia patients with 11q23 abnormalities. , 2000, Leukemia research.

[35]  M. Mancini,et al.  A prospective study of residual-disease monitoring of the ALL1/AF4 transcript in patients with t(4;11) acute lymphoblastic leukemia. , 2000, Blood.

[36]  M. Slovak,et al.  Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. , 2000, Blood.

[37]  M. Cleary,et al.  MLL rearrangements in haematological malignancies: lessons from clinical and biological studies , 1999, British journal of haematology.

[38]  M. Seto,et al.  Chromosome abnormalities and MLL rearrangements in acute myeloid leukemia of infants , 1999, Leukemia.

[39]  J. Nomdedéu,et al.  Adult de novo acute myeloid leukemias with MLL rearrangements. , 1999, Leukemia research.

[40]  C. Bloomfield,et al.  Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. , 1999, Blood.

[41]  R. Berger,et al.  The t(6;11)(q27;q23) translocation in acute leukemia: a laboratory and clinical study of 30 cases , 1998, Leukemia.

[42]  A. Hagemeijer,et al.  The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients , 1998, Leukemia.

[43]  R. Berger,et al.  The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients , 1998, Leukemia.

[44]  A. Moorman,et al.  Hematological malignancies with t(9;11)(p21–22;q23) – a laboratory and clinical study of 125 cases , 1998, Leukemia.

[45]  J. Magaud,et al.  Clinical and biological characteristics of adult de novo and secondary acute myeloid leukemia with balanced 11q23 chromosomal anomaly or MLL gene rearrangement compared to cases with unbalanced 11q23 anomaly: confirmation of the existence of different entities with 11q23 breakpoint , 1998, Leukemia.

[46]  M. Caligiuri,et al.  Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics. , 1998, Cancer research.

[47]  G. Cimino,et al.  ALL1 gene alterations in acute leukemia: biological and clinical aspects. , 1998, Haematologica.

[48]  C. Bloomfield,et al.  Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study. , 1997, Blood.

[49]  C. Bloomfield,et al.  Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study. , 1997, Blood.

[50]  Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Français de Cytogénétique Hématologique. , 1996, Blood.

[51]  A. Hagemeijer,et al.  The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene. , 1995, Blood.

[52]  J. Rowley,et al.  Detection of 11q23/MLL rearrangements in infant leukemias with fluorescence in situ hybridization and molecular analysis. , 1995, Leukemia.

[53]  J. Rowley,et al.  Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[54]  J. Rowley,et al.  Detection of MLL gene rearrangements in adult acute lymphoblastic leukemia. A Cancer and Leukemia Group B study. , 1994, Leukemia.

[55]  Y. Kaneko,et al.  Clinical significance of chromosome abnormalities in childhood acute lymphoblastic leukemia in Japan. , 1994, Leukemia.

[56]  M. Cleary,et al.  ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells. , 1994, Blood.

[57]  M. Caligiuri,et al.  ALL-1 partial duplication in acute leukemia. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[58]  C. Croce,et al.  Sequence analysis of the breakpoint cluster region in the ALL-1 gene involved in acute leukemia. , 1994, Cancer research.

[59]  I. Bernstein,et al.  Molecular rearrangements of the MLL gene are present in most cases of infant acute myeloid leukemia and are strongly correlated with monocytic or myelomonocytic phenotypes. , 1994, The Journal of clinical investigation.

[60]  J. Rowley,et al.  Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA- topoisomerase II , 1993 .

[61]  P. Nowell,et al.  Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation. , 1993, Cancer research.

[62]  M. Seto,et al.  MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13. , 1993, Oncogene.

[63]  J. Rowley,et al.  Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II. , 1993, Blood.

[64]  M. L. Le Beau,et al.  Impact of chromosomal translocations on prognosis in childhood acute lymphoblastic leukemia. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[65]  A. Look,et al.  Chromosomal translocations play a unique role in influencing prognosis in childhood acute lymphoblastic leukemia. , 1986, Blood.