Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study.

نویسندگان

  • Brian V Balgobind
  • Susana C Raimondi
  • Jochen Harbott
  • Martin Zimmermann
  • Todd A Alonzo
  • Anne Auvrignon
  • H Berna Beverloo
  • Myron Chang
  • Ursula Creutzig
  • Michael N Dworzak
  • Erik Forestier
  • Brenda Gibson
  • Henrik Hasle
  • Christine J Harrison
  • Nyla A Heerema
  • Gertjan J L Kaspers
  • Anna Leszl
  • Nathalia Litvinko
  • Luca Lo Nigro
  • Akira Morimoto
  • Christine Perot
  • Rob Pieters
  • Dirk Reinhardt
  • Jeffrey E Rubnitz
  • Franklin O Smith
  • Jan Stary
  • Irina Stasevich
  • Sabine Strehl
  • Takashi Taga
  • Daisuke Tomizawa
  • David Webb
  • Zuzana Zemanova
  • C Michel Zwaan
  • Marry M van den Heuvel-Eibrink
چکیده

Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

MLL gene rearrangement, cytogenetic 11q23 abnormalities, and expression of the NG2 molecule in infant acute myeloid leukemia.

To study prognostic factors in infant acute myeloid leukemia (AML), we analyzed 44 children treated on Childrens Cancer Group protocols for MLL gene rearrangement by Southern blot, cytogenetic 11q23 abnormalities, and reactivity with monoclonal antibody 7.1. This antibody detects the human homologue of the rat NG2 chondroitin sulfate proteoglycan molecule, which has previously been reported to ...

متن کامل

Detection Of 11q23 Gene Rearrangement In Children With Acute Lymphoblastic Leukemia And Its Association With Demographic Data and Response To Initial Chemotherapy On The Seventh Day Of Induction

Background: Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer leading to cancer-related death in children. Most infants with ALL harbor recurring structural chromosomal rearrangements that are important initiating events in leukemogenesis but are insufficient to explain the biology and heterogeneity of the disease. Mixed-lineage leukemia-rearrangement (MLL-rearrange...

متن کامل

Prognostic Value of EVI1 Expression in Pediatric Acute Myeloid Leukemia: A Systematic Review

Acute myeloid leukemia (AML) as a distortion of blood cells involves the differentiation of hematopoietic stem cells. Several studies established the irregular overexpression of specific genes is a common finding in patients with AML. The ectopic viral integration site-1 (EVI1) gene is a proto-oncogene subject to alternative splicing, and encodes a zinc-finger protein that acts as a tr...

متن کامل

The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation Over Chemotherapy Alone in the Treatment of Acute Myeloid Leukemia Patients with Mixed Lineage Leukemia (MLL) Rearrangements

BACKGROUND Acute myeloid leukemia (AML) patients with mixed lineage leukemia (MLL) gene rearrangements always had a very poor prognosis. In this study, we report the incidence of MLL rearrangements in AML patients using gene analysis, as well as the clinical significance and prognostic features of these rearrangements. MATERIAL AND METHODS This retrospective study took place from April 2008 to ...

متن کامل

Cellular drug sensitivity in MLL-rearranged childhood acute leukaemia is correlated to partner genes and cell lineage.

Rearrangements in the 11q23 region, the site of the mixed lineage leukaemia (MLL) gene, are found in both childhood acute myeloid (AML) and lymphoblastic (ALL) leukaemia. We studied the in vitro drug resistance by the fluorometric microculture cytotoxicity assay (FMCA) in 132 children with AML and 178 children with ALL (aged 0-17 years). In AML, children with t(9;11) (n = 10) were significantly...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Blood

دوره 114 12  شماره 

صفحات  -

تاریخ انتشار 2009