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.
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
Shakil H
SH
Merchant
Skip
S
Haines
Bryan
B
Hall
John
J
Hozier
David S
DS
Viswanatha
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