Expression profiles of acute lymphoblastic and myeloblastic leukemias with ALL-1 rearrangements

Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7853-8. doi: 10.1073/pnas.1132115100. Epub 2003 Jun 2.

Abstract

The ALL-1 gene is directly involved in 5-10% of acute lymphoblastic leukemias (ALLs) and acute myeloid leukemias (AMLs) by fusion to other genes or through internal rearrangements. DNA microarrays were used to determine expression profiles of ALLs and AMLs with ALL-1 rearrangements. These profiles distinguish those tumors from other ALLs and AMLs. The expression patterns of ALL-1-associated tumors, in particular ALLs, involve oncogenes, tumor suppressors, antiapoptotic genes, drug-resistance genes, etc., and correlate with the aggressive nature of the tumors. The genes whose expression differentiates between ALLs with and without ALL-1 rearrangement were further divided into several groups, enabling separation of ALL-1-associated ALLs into two subclasses. One of the groups included 43 genes that exhibited expression profiles closely linked to ALLs with ALL-1 rearrangements. Further, there were evident differences between the expression profiles of AMLs in which ALL-1 had undergone fusion to other genes and AMLs with partial duplication of ALL-1. The extensive analysis described here pinpointed genes that might have a direct role in pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosome Aberrations
  • Chromosomes, Human, Pair 11
  • Chromosomes, Human, Pair 4
  • Cluster Analysis
  • DNA-Binding Proteins / genetics*
  • Down-Regulation
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia, Myeloid, Acute / blood*
  • Leukemia, Myeloid, Acute / genetics*
  • Myeloid-Lymphoid Leukemia Protein
  • Oligonucleotide Array Sequence Analysis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Proto-Oncogenes*
  • Transcription Factors*
  • Transcription, Genetic
  • Translocation, Genetic*
  • Up-Regulation

Substances

  • DNA-Binding Proteins
  • KMT2A protein, human
  • Transcription Factors
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase