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Molecular emergence of acute myeloid leukemia during treatment for acute lymphoblastic leukemia.

Abstract：

:Therapy-related acute myeloid leukemias (t-AML) with translocations of the MLL gene are associated with the use of topoisomerase II inhibitors. We established the emergence of the malignant clone in a child who developed t-AML with a t(11;19) (q23;p13.3) during treatment for acute lymphoblastic leukemia (ALL). The MLL-ENL and the reciprocal ENL-MLL genomic fusions and their chimeric transcripts were characterized from samples collected at the time of t-AML diagnosis. We used PCR with patient-specific genomic primers to establish the emergence of the MLL-ENL fusion in serially obtained DNA samples. The MLL-ENL fusion was not detectable in bone marrow at the time of ALL diagnosis or after 2 months of chemotherapy (frequency <8.3 x 10(-7) cells(-1)). The genomic fusion was first detected in bone marrow after 6 months of treatment at a frequency of one in 4,000 mononuclear bone marrow cells; the frequency was one in 70 cells after 20 months of therapy. At the first detection of MLL-ENL, the only topoisomerase II inhibitors the patient had received were one dose of daunorubicin and two doses of etoposide. The MLL-ENL fusion was not detectable in blood at the time of ALL diagnosis or after 0.7, 2, 8, 10, and 12 months of therapy but was detectable in blood at 16 months (one in 2.3 x 10(4) cells). Recombinogenic Alu sequences bracketed the breakpoints in both fusions. These data indicate that the malignant clone was not present before therapy, arose early during chemotherapy, and was able to proliferate even during exposure to antileukemic therapy.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Blanco JG,Dervieux T,Edick MJ,Mehta PK,Rubnitz JE,Shurtleff S,Raimondi SC,Behm FG,Pui CH,Relling MV

doi

10.1073/pnas.181199898

keywords:

subject

Has Abstract

pub_date

2001-08-28 00:00:00

pages

10338-43

issue

18

eissn

0027-8424

issn

1091-6490

pii

98/18/10338

journal_volume

98

pub_type

杂志文章

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