Is it important to decipher the heterogeneity of "normal karyotype AML"? Journal Article
| Author: | Nimer, S. D. |
| Article 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. © 2007 Elsevier Ltd. All rights reserved. |
| Keywords: | cancer survival; unclassified drug; acute granulocytic leukemia; gene mutation; overall survival; mutation; leukemia, myeloid, acute; histone deacetylase inhibitor; clinical trial; neutropenia; review; fluorouracil; dose response; drug efficacy; nonhuman; adjuvant therapy; cancer adjuvant therapy; drug megadose; bcg vaccine; cancer immunotherapy; enzyme inhibition; gene expression; granulocyte macrophage colony stimulating factor; gene product; cytogenetics; drug resistance, neoplasm; enzyme activity; cancer resistance; stem cell; molecular mechanics; methyltransferase; neoplasm, residual; histone methyltransferase; hematopoietic stem cells; chromosome translocation; hematopoietic stem cell; gene silencing; chromosome aberrations; drug treatment failure; karyotype; karyotyping; granulocyte colony stimulating factor; histone deacetylase; genetic heterogeneity; leukemia remission; npm; aml; tandem repeat sequences; cd135 antigen; nucleophosmin; erg; dna methyltransferase inhibitor; transcription factor elf 1; baalc; c/ebp-α; flt3-itd; mll-ptd; brain and acute leukemia cytoplasmic protein; ccaat enhancer binding protein alpha |
| Journal Title: | Best Practice and Research: Clinical Haematology |
| Volume: | 21 |
| Issue: | 1 |
| ISSN: | 1521-6926 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2008-03-01 |
| Start Page: | 43 |
| End Page: | 52 |
| Language: | English |
| DOI: | 10.1016/j.beha.2007.11.010 |
| PUBMED: | 18342811 |
| PROVIDER: | scopus |
| PMCID: | PMC2654590 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 17 November 2011" - "CODEN: BPRCA" - "Source: Scopus" |
