The specificity of immunophenotypic alterations in blasts in nonacute myeloid disorders

Alexandra Harrington1, Horatiu Olteanu, Steven Kroft

  • 1Dept of Pathology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA.

Insights

Flow cytometry (FC) analysis of myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), and chronic myelomonocytic leukemias (CMMLs) reveals shared immunophenotypic alterations in blasts. Differentiating neoplastic from nonneoplastic myeloid disorders requires careful comparison with reactive bone marrow samples.

Area of Science:

  • Hematology
  • Immunology
  • Oncology

Background:

  • Flow cytometry (FC) analysis for non-acute myeloid disorders is challenged by inconsistent gating and limited controls.
  • Existing controls often rely solely on normal bone marrow (BM) samples, potentially obscuring subtle neoplastic changes.

Purpose of the Study:

  • To compare blast immunophenotypes in myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), and chronic myelomonocytic leukemias (CMMLs) against nonneoplastic controls.
  • To identify specific immunophenotypic alterations that distinguish neoplastic myeloid disorders from reactive conditions.

Main Methods:

  • Utilized 4-color FC to analyze blasts from diagnostic BM samples of MDSs, MPNs, and CMMLs.
  • Compared these neoplastic samples against 20 nonneoplastic cytopenias/cytoses (CCs) and negative staging BM samples.

Main Results:

  • Blasts in 10 of 20 nonneoplastic cytopenias/cytoses (CCs) exhibited immunophenotypic differences compared to control samples.
  • Immunophenotypic alterations were found in a significant proportion of MDSs (18/21), MPNs (11/14), and CMMLs (7/7) versus control samples.
  • Compared to CCs, neoplastic samples showed alterations in 62% of MDSs, 50% of MPNs, and 43% of CMMLs. Neoplastic-specific changes included aberrant expression of CD7, CD11b, CD15, CD36, CD56, CD34 overexpression, and variable HLA-DR.

Conclusions:

  • Several blast immunophenotypic alterations are shared between neoplastic and nonneoplastic bone marrow samples, complicating diagnosis.
  • Approximately 40% to 60% of neoplastic bone marrow samples displayed aberrant immunophenotypes not observed in reactive bone marrow samples.
  • Distinguishing neoplastic myeloid disorders requires careful evaluation of blast immunophenotypes against both normal and reactive nonneoplastic controls.