The pathogenesis of mixed-lineage leukemia

Andrew G. Muntean, Jay Hess

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

Aggressive leukemias arise in both children and adults as a result of rearrangements to the mixed-lineage leukemia gene (MLL) located on chromosome 11q23. MLL encodes a large histone methyltransferase that directly binds DNA and positively regulates gene transcription, including homeobox (HOX) genes. MLL is involved in chromosomal translocations, partial tandem duplications, and amplifications, all of which result in hematopoietic malignancies due to sustained HOX expression and stalled differentiation. MLL lesions are associated with both acute myeloid leukemia and acute lymphoid leukemia and are usually associated with a relatively poor prognosis despite improved treatment options such as allogeneic hematopoietic stem cell transplantation, which underscores the need for new treatment regimens. Recent advances have begun to reveal the molecular mechanisms that drive MLL-associated leukemias, which, in turn, have provided opportunities for therapeutic development. Here, we discuss the etiology of MLL leukemias and potential directions for future therapy.

Original languageEnglish (US)
Pages (from-to)283-301
Number of pages19
JournalAnnual Review of Pathology: Mechanisms of Disease
Volume7
DOIs
StatePublished - 2012
Externally publishedYes

Fingerprint

leukemia
Leukemia
pathogenesis
Genes
genes
Homeobox Genes
Genetic Translocation
Hematopoietic Stem Cell Transplantation
myeloid leukemia
therapeutics
cell transplantation
homeotic genes
Hematologic Neoplasms
Therapeutics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
methyltransferases
Acute Myeloid Leukemia
histones
prognosis
etiology

Keywords

  • Epigenetics
  • Histone methylation
  • Therapeutics
  • Transcription
  • Translocation

ASJC Scopus subject areas

  • Plant Science

Cite this

The pathogenesis of mixed-lineage leukemia. / Muntean, Andrew G.; Hess, Jay.

In: Annual Review of Pathology: Mechanisms of Disease, Vol. 7, 2012, p. 283-301.

Research output: Contribution to journalArticle

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