Expression profiling of murine acute promyelocytic leukemia cells reveals multiple model-dependent progression signatures.

Abstract:

:Leukemia results from the expansion of self-renewing hematopoietic cells that are thought to contain mutations that contribute to disease initiation and progression. Studies of the gene expression profiles of human acute myeloid leukemia samples has allowed their classification based on the presence of translocations and French-American-British subtypes, but it is not yet clear whether their molecular signatures reflect the initiating mutations or mutations acquired during progression. To begin to address this question, we examined the expression profiles of normal murine promyelocyte-enriched samples, nontransformed murine promyelocytes expressing human promyelocytic leukemia-retinoic acid receptor alpha (PML-RARalpha) fusion gene, and primary acute promyelocytic leukemia cells. The expression profile of nontransformed cells expressing PML-RARalpha was remarkably similar to that of wild-type promyelocytes. In contrast, the expression profiles of fully transformed cells from three acute promyelocytic leukemia model systems were all different, suggesting that the expression signature of acute promyelocytic leukemia cells reflects the genetic changes that contributed to progression. To further evaluate these progression events, we compared two high-penetrance acute promyelocytic leukemia models that both commonly acquire an interstitial deletion of chromosome 2 during progression. The two models exhibited distinct gene expression profiles, suggesting that the dominant molecular signatures of murine acute promyelocytic leukemia can be influenced by several independent progression events.

journal_name

Mol Cell Biol

authors

Walter MJ,Park JS,Lau SK,Li X,Lane AA,Nagarajan R,Shannon WD,Ley TJ

doi

10.1128/MCB.24.24.10882-10893.2004

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

10882-93

issue

24

eissn

0270-7306

issn

1098-5549

pii

24/24/10882

journal_volume

24

pub_type

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