Related Experiment Videos
Expression of cell-surface antigens in acute promyelocytic leukaemia
1New York Medical College, Valhalla, NY, USA. epaietta@earthlink.net
Abstract:
Acute promyelocytic leukaemia (APL) with M3 (or M3v) morphology is the only AML subtype to date for which morphology and immunophenotype agree. In other words, FAB M3 is interchangeable with a unique marker profile. More precisely, we have finally recognized a surrogate marker profile for leukaemia derived from the (15;17) translocation and expressing PML/RARalpha transcripts. To present this as a new development may come as a surprise to many. After all, the antigen expression pattern of AML-M3 was well recognized for many years: absence or weak expression of HLA-DR, CD117, CD15, CD11b and CD34 in the context of a myeloid phenotype (CD33 and CD13 expression) and frequently associated with moderate to high side-scatter appearance upon flow cytometric evaluation, depending upon the degree of granularity of the leukaemic cells. While partially correct, this established APL phenotype is both flawed and limited in its ability to distinguish APL from other AML subtypes, such as natural-killer-cell AML. Given the availability of phenotype-specific therapy for APL, such as all-trans retinoic acid or arsenic trioxide, failing to diagnose APL or misdiagnosing a case of AML with an APL-like phenotype will result in serious clinical consequences. Faced with this dilemma, we have recently performed a comprehensive immunophenotypic analysis of APL patients entered on Eastern Cooperative Oncology Group trials. Our results give diagnostic power to only three antigens, HLA-DR, CD11a and CD18, all of which are characteristically expressed at low levels by APL cells. Despite some significant antigenic differences (e.g. in CD34 expression), this surrogate marker profile for t(15;17) APL applies to both the M3 and the M3v FAB phenotypes and to all three isoforms of the PML/RARalpha transcript.
Insights
Acute promyelocytic leukemia (APL) diagnosis is improved by identifying a unique immunophenotypic marker profile. This profile aids in distinguishing APL from other acute myeloid leukemia subtypes, ensuring accurate treatment.
Area of Science:
- Hematology
- Immunophenotyping
- Leukemia Research
Background:
- Acute promyelocytic leukemia (APL), or FAB M3, is unique in AML for matching morphology and immunophenotype.
- Previous understanding of APL's antigen expression was limited and could be confused with other AML subtypes.
- Accurate APL diagnosis is critical due to targeted therapies like all-trans retinoic acid and arsenic trioxide.
Purpose of the Study:
- To define a reliable immunophenotypic surrogate marker profile for APL.
- To improve the diagnostic accuracy of APL, especially differentiating it from AML subtypes with similar phenotypes.
- To validate this profile for both M3 and M3v FAB phenotypes and PML/RARalpha transcript variants.
Main Methods:
- Comprehensive immunophenotypic analysis of APL patients.
- Evaluation of antigen expression patterns using flow cytometry.
- Comparison of APL immunophenotypes with other AML subtypes.
Main Results:
- A specific surrogate marker profile for APL, linked to the t(15;17) translocation and PML/RARalpha transcripts, was identified.
- Low expression of HLA-DR, CD11a, and CD18 proved to be the most diagnostically powerful markers for APL.
- This profile is consistent across M3 and M3v FAB phenotypes and different PML/RARalpha transcript isoforms.
Conclusions:
- The identified immunophenotypic profile provides a robust method for diagnosing APL.
- Accurate identification of APL is crucial for initiating timely and appropriate phenotype-specific therapies.
- This finding refines the understanding of APL immunophenotype, aiding in clinical diagnostics and research.