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Detection of minimal residual disease in acute myelomonocytic leukemia with
abnormal marrow eosinophils by nested polymerase chain reaction with allele
specific amplification
J Hebert, JM Cayuela, MT Daniel, R Berger and F Sigaux
Laboratoire d'Hematologie Moleculaire, Hopital Saint-Louis, Paris, France.
Acute myelomonocytic leukemia with bone marrow eosinophilia (AML-M4Eo in
the French-American-British FAB] classification) is frequently associated
with pericentric inversion of chromosome 16, inv(16)(p13q22). Recently, the
molecular cloning of teh breakpoints has led to the identification of the
two fused genes, CBFB on 16q and MYH11 on 16p. We have analyzed 24 patients
with AML-M4Eo at diagnosis and 47 patients with AML of other FAB subtypes,
by a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for the
CBFB/MYH11 fusion mRNAs. Three types of fusion mRNAs were detected in 22
samples of AML- M4Eo (type A, n = 20; type C, n = 1; and type D, n = 1).
Among these 22 positive samples, inv(16) was found in the 20
cytogenetically studied cases. No fusion transcript was detected in two
patients with AML-M4Eo and in patients with other types of AML. These
results confirm that CBFB/MYH11 transcripts (with a predominant type A
form) are present in most cases of inv(16) AML. Moreover, detection of the
hybrid transcript is closely associated with the finding of abnormal bone
marrow (BM) eosinophils in AML-M4Eo as it is not found in other, FAB
subtypes of AML, including AML-M4. To assess the presence of type A
CBFB/MYH11 fusion transcripts in five AML-M4Eo patients in remission, we
designed a sensitive assay combining nested PCR and allele-specific
amplification (NPASA). Residual leukemia cells were detected in four
patients who were in remission from 4 to 22 months, but not in one patient
in long-term remission (5 years). The clinical relevance of persistent
CBFB/MYH11 fusion transcripts in remission remains to be established by
studying a large prospective series of patients. NPASA provides a useful
and sensitive tool for the detection of minimal residual disease in inv(16)
AML and, potentially, in other leukemias associated with translocations
that result in a predominant fusion transcript.
Volume 84,
Issue 7,
pp. 2291-2296,
10/01/1994
Copyright © 1994 by The American Society of Hematology
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