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Activating mutations in NOTCH1 in acute myeloid leukemia and lineage switch leukemias.

Abstract：

:Activating mutations in NOTCH1 are found in over 50% of human T-cell lymphoblastic leukemias (T-ALLs). Here, we report the analysis for activating NOTCH1 mutations in a large number of acute myeloid leukemia (AML) primary samples and cell lines. We found activating mutations in NOTCH1 in a single M0 primary AML sample, in three (ML1, ML2 and CTV-1) out of 23 AML cell lines and in the diagnostic (myeloid) and relapsed (T-lymphoid) clones in a patient with lineage switch leukemia. Importantly, the ML1 and ML2 AML cell lines are derived from an AML relapse in a patient initially diagnosed with T-ALL. Overall, these results demonstrate that activating mutations in NOTCH1 are mostly restricted to T-ALL and are rare in AMLs. The presence of NOTCH1 mutations in myeloid and T-lymphoid clones in lineage switch leukemias establishes the common clonal origin of the diagnostic and relapse blast populations and suggests a stem cell origin of NOTCH1 mutations during the molecular pathogenesis of these tumors.

journal_name

Leukemia

journal_title

Leukemia

authors

Palomero T,McKenna K,O-Neil J,Galinsky I,Stone R,Suzukawa K,Stiakaki E,Kalmanti M,Fox EA,Caligiuri MA,Aster JC,Look AT,Ferrando AA

doi

10.1038/sj.leu.2404409

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

1963-6

issue

11

eissn

0887-6924

issn

1476-5551

pii

2404409

journal_volume

20

pub_type

杂志文章

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