Fluorescence in situ hybridization identifies cryptic t(16;16)(p13;q22) masked by del(16)(q22) in a case of AML-M4 Eo.
We report a patient presenting with acute myeloid leukemia (AML)-M4 Eo, in whom conventional cytogenetic analysis revealed a 46, XY, del(16)(q22) karyotype. Molecular analysis of the bone marrow cells using reverse transcriptase polymerase chain reaction (RT-PCR) identified a CBFbeta-MYH11, "type A" fusion transcript. However, despite a thorough reevaluation, a balanced chromosome 16 abnormality could not be definitively identified by cytogenetics. Since there exists a small possibility of obtaining a false-positive PCR result, fluorescence in situ hybridization (FISH) analysis using dual-color, break-apart probes for CBFbeta was performed to elucidate the mechanism of fusion gene formation and thus confirm the RT-PCR results. FISH analysis clearly revealed a cryptic t(16;16), which was probably masked by the del(16)(q22). FISH is the preferred diagnostic procedure to elucidate the CBFbeta-MYH11 fusion in this situation, and resolves the possibility of both false-positive and false-negative results with RT-PCR technique. Due to the improved prognosis of AML associated with the CBFbeta-MYH11 fusion compared to AML generally, we recommend the use of FISH for detection of inv(16)/t(16;16)/CBFbeta-MYH11 in patients with failed, complex, or apparently normal cytogenetics, and in whom the cell morphology indicates the strong possibility of this gene fusion.
Merchant
Shakil H
SH
University of New Mexico Health Sciences Center, Department of Pathology, BRF Room 337C, 915 Camino de Salud, NE, Albuquerque, NM 87131. dviswanatha@salud.unm.edu
Haines
Skip
S
Hall
Bryan
B
Hozier
John
J
Viswanatha
David S
DS
D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004804:Eosinophils / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic
C095514:CBFbeta-MYH11 fusion protein; D015514:Oncogene Proteins, Fusion