Positive selection for CD90 as a purging option in acute myeloid leukemia stem cell transplants

Cytometry B Clin Cytom. 2008 Jan;74(1):9-16. doi: 10.1002/cyto.b.20375.

Abstract

Background: Several studies showed the benefit of purging of acute myeloid leukemia (AML) stem cell transplants. We reported previously that purging by positive selection of CD34+ and CD133+ cells resulted in a 3-4 log tumor cell reduction (TCR) in CD34- and/or CD133- AML, but has been shown to be potentially applicable in only about 50% of cases. Similar to CD34 and CD133, CD90 marks the hematopoietic CD34 positive stem cells capable of full hematopoietic recovery after myeloablative chemotherapy, and therefore, in the present study, we explored whether a similar purging approach is possible using CD90.

Methods: CD90 expression was established by flowcytometry in diagnosis AML on the clonogenic AML CD34+ blast population by flow cytometry. Positivity was defined as >3% CD90 (CD34+) expression on blasts. For the calculation of the efficacy of TCR by positive selection, AML blasts were recognized by either prelabeling diagnosis blasts with CD45-FITC in spiking model experiments or using expression of leukemia associated marker combinations both in spiking experiments and in real transplants.

Results: In 119 patients with AML and myelodysplastic syndrome, we found coexpression of CD34 and CD90 (>3%) in 42 cases (35%). In AML patients 60 years or younger, representing the patients who are eligible for transplantation, only 23% (16/69) of the patients showed CD90 expression. Positive selection for CD90 in transplants containing CD90 negative AML resulted in a 2.8-4 log TCR in the models used.

Conclusions: Purging by positive selection using CD90 can potentially be applied effectively in the majority of AML patients 60 years or younger.

MeSH terms

  • Antigens, CD34 / immunology
  • Antigens, CD34 / metabolism
  • Biomarkers, Tumor / immunology
  • Bone Marrow Purging / methods*
  • Female
  • Flow Cytometry*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / methods*
  • Thy-1 Antigens / immunology*

Substances

  • Antigens, CD34
  • Biomarkers, Tumor
  • Thy-1 Antigens