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Variant three-way translocation of inversion 16 in AML-M4Eo confirmed by fluorescence in situ hybridization analysis
J A Martinez-Climent1, A M Comes, E Vizcarra
1Department of Hematology and Oncology, Hospital Clinico Universitario, University of Valencia, Spain.
Abstract:
The inv(16) and t(16;16) characterize a subgroup of acute myelomonocytic leukemia (AML) with distinct morphological features and a favorable prognosis. Both cytogenetic abnormalities result in a fusion of CBF beta at 16q22 and MYH11 gene at 16p13, whose detection by PCR and fluorescence in situ hybridization (FISH) is useful for diagnosis and monitoring of the disease. Variant translocations of inv(16)/t(16;16) are very rare and whether they are also associated with a favorable prognosis is unknown. We report a patient presenting with typical AML-M4Eo and a three-way translocation of inv(16) involving 16p13, 16q22, and 3q22. FISH studies on bone marrow (BM) chromosomes using CBFB and MYH11 DNA probes revealed a fusion of CBFB and MYH11 on 16q of the der(16), as well as a signal from MYH11 on 16p but not from CBFB; normal signals for both probes were present on the normal 16. Neither of these labeled probes was on the der(3), but the translocation between the der(3) and der(16) was confirmed by using a chromosome 16 painting probe. Molecular analysis of BM cells using RT-PCR identified a CBFB-MYH11 fusion transcript type D. After achieving complete remission, the patient relapsed. We conclude that FISH and PCR are feasible tools to distinguish cases with variant abnormalities of inv(16) from cases with other chromosome 16 abnormalities. Variant abnormalities of inv(16) may be not associated with favorable prognosis.
Insights
Variant chromosome 16 abnormalities in acute myelomonocytic leukemia (AML) may not confer a favorable prognosis. Molecular and FISH analyses are crucial for diagnosing rare inv(16) cases.
Area of Science:
- Hematology
- Cytogenetics
- Molecular Biology
Background:
- The inv(16) and t(16;16) chromosomal abnormalities are hallmarks of a specific acute myelomonocytic leukemia (AML) subtype, typically associated with favorable prognosis.
- These abnormalities lead to the fusion of the CBFB gene (16q22) and MYH11 gene (16p13), detectable by PCR and FISH for diagnosis and monitoring.
Observation:
- This report details a rare case of AML-M4Eo with a three-way translocation involving chromosome 16 (inv(16)) and chromosome 3.
- FISH and RT-PCR confirmed a CBFB-MYH11 fusion transcript (type D) in the patient's bone marrow cells.
Findings:
- Despite initial complete remission, the patient relapsed, suggesting that this variant translocation may not share the favorable prognosis of standard inv(16).
- FISH and PCR proved effective in differentiating this variant inv(16) from other chromosome 16 abnormalities.
Implications:
- This case highlights the importance of detailed cytogenetic and molecular analysis for accurate diagnosis and prognosis in AML.
- Variant inv(16) translocations may represent a distinct prognostic category within AML, warranting further investigation.