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Published on: March 26, 2018
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.
Abstract:
Data regarding flow cytometry (FC) in nonacute myeloid disorders is confounded by variable gating strategies and controls limited to normal bone marrow (BM) samples. Blasts in diagnostic BM samples of myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), and chronic myelomonocytic leukemias (CMMLs) were compared with 20 nonneoplastic cytopenias/cytoses (CCs) and negative staging BM samples using 4-color FC. Blasts in 10 of 20 CCs showed immunophenotypic differences vs control samples. Immunophenotypic alterations were identified in 18 of 21 MDSs, 11 of 14 MPNs, and 7 of 7 CMMLs vs control samples and 13 (62%) of 21 MDSs, 7 (50%) of 14 MPNs, and 3 (43%) of 7 CMMLs vs CCs. Neoplastic-specific blast immunophenotypic changes included expression of CD7, CD11b, CD15, CD36, and CD56; CD34 overexpression; HLA-DR variability; lack of CD13 and CD33; underexpression of CD13, CD33, CD45, and HLA-DR; and partial loss of CD13, CD33, CD38, and CD117. In all cases, blasts were CD34+. Several blast immunophenotypic alterations are shared in neoplastic and nonneoplastic BM samples. Approximately 40% to 60% of neoplastic BM samples exhibited aberrancies not seen in reactive BM samples.
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