Is it important to decipher the heterogeneity of "normal karyotype AML"?

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalBest Practice and Research: Clinical Haematology
Volume21
Issue number1
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Karyotype
Acute Myeloid Leukemia
Mutation
Leukemia
Stem cells
Bone
Cells
Recurrence
Messenger RNA
Genetic Heterogeneity
Chromosome Aberrations
Bone Marrow Cells
Stem Cells
Population
nucleophosmin
Therapeutics

Keywords

  • AML
  • BAALC
  • C/EBP-α
  • cytogenetics
  • ERG
  • FLT3-ITD
  • histone deacetylase
  • methyltransferase
  • MLL-PTD
  • NPM
  • stem cell

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Is it important to decipher the heterogeneity of "normal karyotype AML"? / Nimer, Stephen D.

In: Best Practice and Research: Clinical Haematology, Vol. 21, No. 1, 01.03.2008, p. 43-52.

Research output: Contribution to journalArticle

@article{11cf2d1a910c4fd3bf7a8465adb3b72e,
title = "Is it important to decipher the heterogeneity of {"}normal karyotype AML{"}?",
abstract = "Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet {"}normal karyotype AML{"} lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in {"}normal karyotype AML{"} is leading to more targeted approaches to develop more effective treatments for this disease.",
keywords = "AML, BAALC, C/EBP-α, cytogenetics, ERG, FLT3-ITD, histone deacetylase, methyltransferase, MLL-PTD, NPM, stem cell",
author = "Nimer, {Stephen D}",
year = "2008",
month = "3",
day = "1",
doi = "10.1016/j.beha.2007.11.010",
language = "English",
volume = "21",
pages = "43--52",
journal = "Best Practice and Research in Clinical Haematology",
issn = "1521-6926",
publisher = "Bailliere Tindall Ltd",
number = "1",

}

TY - JOUR

T1 - Is it important to decipher the heterogeneity of "normal karyotype AML"?

AU - Nimer, Stephen D

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease.

AB - Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease.

KW - AML

KW - BAALC

KW - C/EBP-α

KW - cytogenetics

KW - ERG

KW - FLT3-ITD

KW - histone deacetylase

KW - methyltransferase

KW - MLL-PTD

KW - NPM

KW - stem cell

UR - http://www.scopus.com/inward/record.url?scp=40749159082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40749159082&partnerID=8YFLogxK

U2 - 10.1016/j.beha.2007.11.010

DO - 10.1016/j.beha.2007.11.010

M3 - Article

C2 - 18342811

AN - SCOPUS:40749159082

VL - 21

SP - 43

EP - 52

JO - Best Practice and Research in Clinical Haematology

JF - Best Practice and Research in Clinical Haematology

SN - 1521-6926

IS - 1

ER -