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Myeloblasts in normal bone marrows expressing leukaemia-associated immunophenotypes.

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Normal myeloblasts can express leukaemia-associated immunophenotypes (LAIP), impacting acute myeloid leukaemia (AML) measurable residual disease (MRD) test specificity. Understanding normal myeloblast profiles is crucial for accurate AML MRD detection.

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Area of Science:

  • Hematology
  • Immunophenotyping
  • Clinical Diagnostics

Background:

  • Measurable residual disease (MRD) status is critical for acute myeloid leukaemia (AML) prognosis and treatment guidance.
  • Multicolour flow cytometry (MCF) is a sensitive method for MRD detection.
  • Current AML MRD detection relies on leukaemia-associated immunophenotypes (LAIP) or aberrant differentiation profiles, but normal myeloblast expression of LAIP challenges specificity.

Purpose of the Study:

  • To investigate the expression of LAIP on normal adult myeloblasts.
  • To assess the impact of normal myeloblast LAIP on the specificity of AML MRD detection.
  • To provide data for optimizing AML MRD diagnostic cut-offs.

Main Methods:

  • Analysis of 14 normal adult bone marrow samples using 4-colour flow cytometry.
  • Assessment of CD15, CD11b, CD7, CD4, and CD56 expression on CD34+ myeloblasts.
  • Evaluation of LAIP defined by lineage infidelity or asynchronous differentiation markers.

Main Results:

  • Normal myeloblasts exhibited LAIP in 43% to 100% of cases, depending on the markers used and cut-off levels.
  • Even at a 0.1% threshold, false positive MRD results can occur due to aberrant CD15 or CD7 expression on normal cells.
  • Findings highlight limitations in specificity for AML MRD detection using current LAIP criteria.

Conclusions:

  • The expression of LAIP on normal myeloblasts significantly affects the specificity of AML MRD detection.
  • Establishing a collaborative database of LAIP on normal myeloblasts with standardized analysis is essential.
  • Optimized diagnostic cut-offs are needed to improve the accuracy of AML MRD determination.