Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) form a heterogeneous group of clonal hematopoietic disorders with unfavourable prognosis. Allogeneic bone marrow transplantation is the only potentially curative treatment, but remains limited to a small subgroup of younger patients with HLA-compatible donors. As autologous stem cell transplantation is currently being explored as an alternative treatment strategy for MDS, more information needs to be acquired regarding the clonal nature of the progenitor cells in these autografts. Therefore, we have analyzed the clonal patterns of highly purified hematopoietic progenitors and their mature daughter cells in mobilized peripheral blood collections produced from five female patients with high-risk MDS in complete hematologic remission. X-chromosome activation patterns of flow-sorted immature (CD34 + 38low, CD34 + 33low) and committed (CD34 + 38high, CD34 + 33high) progenitors were studied with the polymerase chain reaction-based HUMARA assay. In four patients, a polyclonal remission was shown in all stem cell subpopulations and their mature daughter cells whereas one patient was found to remain skewed in all fractions, except T lymphocytes. This study provides strong evidence that polyclonal immature hematopoietic progenitors can be mobilized and harvested in patients high-risk MDS after treatment with high-dose chemotherapy.
Delforge
M
M
Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium.
Demuynck
H
H
Vandenberghe
P
P
Verhoef
G
G
Zachée
P
P
van Duppen
V
V
Marijnen
P
P
Van den Berghe
H
H
Boogaerts
M A
MA
D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D001853:Bone Marrow / Q000187:drug effects; D002469:Cell Separation; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells / Q000187:drug effects / Q000473:pathology*; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000008:administration & dosage; D004303:Dosage Compensation, Genetic; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D000078224:Lenograstim; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012306:Risk; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D011994:Recombinant Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D008942:Mitoxantrone; D000069585:Filgrastim