Genomic amplification of MYC as double minutes in a patient with APL-like leukemia.
BACKGROUND
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by a PML-RARA fusion due to a translocation t(15;17). Its sensitivity to treatment with all-trans retinoic acid (ATRA), which causes differentiation of the abnormal promyelocytes, combined with anthracycline based chemotherapy makes it the best curable subtype of acute myeloid leukemia. A rapid and accurate diagnosis is needed in the first place to prevent (more) bleeding problems. Here we present a patient with a leukemia with an APL-like morphology but no detectable PML-RARA fusion, as demonstrated by RT-PCR and cytogenetic analysis.


RESULTS
Unexpectedly, karyotyping revealed numerous double minutes (dmins). Fluorescence in situ hybridization (FISH) with DNA probes specific for the MYC-region showed the presence of multiple MYC amplicons. SNP-array analysis uncovered amplification of the 8q24.13-q24.21 region, including the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same chromosome region.


CONCLUSIONS
The diagnosis was revised to AML, not otherwise specified (AML, NOS) and therefore therapy with ATRA was discontinued.
Department of Clinical Genetics, VU University Medical Center, De Boelelaan 1117, PK 0X011, Amsterdam, 1081 HV The Netherlands.
Pino J
PJ
Poddighe
Department of Clinical Genetics, VU University Medical Center, De Boelelaan 1117, PK 0X011, Amsterdam, 1081 HV The Netherlands.
Hans
H
Wessels
Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands.
Pauline
P
Merle
Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands.
Marisa
M
Westers
Department of Clinical Genetics, VU University Medical Center, De Boelelaan 1117, PK 0X011, Amsterdam, 1081 HV The Netherlands.
Shama
S
Bhola
Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands.
Anne
A
Loonen
Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands.
Sonja
S
Zweegman
Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands.
Gert J
GJ
Ossenkoppele
Department of Haematology, VU University Medical Center, Amsterdam, The Netherlands.
Marielle J
MJ
Wondergem
Acute promyelocytic leukemia; Cytogenetics; Double minutes; MYC; SNP-array