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Variant complex translocations involving chromosomes 1, 9, 9, 15 and 17 in acute promyelocytic leukemia without RAR
S K Gogineni1, H O Shah, M Chester
1Division of Genetics, Long Island College Hospital-SUNY, Health Science Center at Brooklyn 11201-5514, USA.
Abstract:
Acute promyelocytic leukemia (APL;M3) is specifically characterized by a predominance of malignant promyelocytes having atypical reciprocal translocation involving chromosome 15 and 17 [t(15;17)(q22;q11)] resulting in the fusion of retinoic acid receptor alpha (RAR alpha) on chromosome 17 and the putative transcription factor gene PML, ie the translocation generates two fusion transcripts, PML/RAR alpha and RAR alpha/PML. We describe a patient with clinical and morphologic characteristics of atypical APL but with a previously undescribed variant translocation. A 35-year-old Hispanic having atypical APL was referred for cytogenetic evaluation. The cytogenetic findings with GTG-banding coupled with FISH analysis revealed the following karyotype: 46,XX,der(9)t(1;9)(q25;q34)der(9)t(9;?)(q34;?), t(15;17)(q22;q11)ish. der(9)t(1;9)(q25;q34)(WCP1+,WCP9+),t(9;17;15)(q34;q11;q22) (WCP9+,WCP15+,PML+;WCP17+,RAR alpha +;WCP15+,WCP17+,PML-)[20]/46,XX[5]. The chromosome 17q was translocated to the chromosome 15q. However, chromosome 15q including the PML gene normally translocating to 17q and creating the RAR alpha/PML fusion gene, translocated to chromosome 9q. Does this patient have another subset of APL? Or is the genetics of APL different in cases with variant translocations as opposed to those with atypical t(15;17) translocation, though in the majority of the cases their clinical presentation remains the same.
Insights
Acute promyelocytic leukemia (APL) typically involves a t(15;17) translocation. This study details a unique variant translocation in an atypical APL case, questioning the established genetic mechanisms of APL.
Area of Science:
- Hematology
- Cancer Genetics
- Cytogenetics
Background:
- Acute promyelocytic leukemia (APL) is defined by malignant promyelocytes and a characteristic t(15;17) translocation.
- This translocation fuses the retinoic acid receptor alpha (RAR alpha) and PML genes, creating PML/RAR alpha and RAR alpha/PML fusion transcripts.
Observation:
- A patient presented with clinical and morphological features of atypical APL.
- Cytogenetic and FISH analysis revealed a novel variant translocation involving chromosomes 1, 9, 15, and 17.
Findings:
- The standard t(15;17) translocation was observed, but with a unique rearrangement.
- The PML gene on chromosome 15q translocated to 9q, while RAR alpha on 17q translocated to 15q, deviating from the typical fusion pattern.
Implications:
- This case suggests a potential new subset of APL or highlights genetic diversity in APL with variant translocations.
- Further research is needed to understand if these genetic variations impact APL's clinical presentation or treatment outcomes.