Clonal hematopoiesis in patients with acquired aplastic anemia.
To determine whether patients with acquired asplastic anemia (AA) exhibit clonal hematopoiesis, we used restriction fragment length polymorphisms of the X-linked genes phosphoglycerate kinase (PGK1) and hypoxanthine phosphoribosyltransferase (HPRT) and the X-linked probe M27 beta. Of the 19 female patients studied, 18 (95%) patients were informative for at least one marker. Of these, eight patients (42%) were heterozygous for PGK1, two (11%) for HPRT, and 16 (84%) for M27 beta. In 13 (72%) patients, a monoclonal pattern was found. Analysis of purified cell suspensions of four of these patients showed that both myeloid and lymphoid cells were of monoclonal origin, indicating the involvement of an early stem cell. The four patients who were studied at presentation all showed a monoclonal pattern. One of these patients showed a spontaneous recovery despite persistent clonal hematopoiesis. The presence of either clonal or polyclonal hematopoiesis did not show a correlation with the response to antithymocyte globulin (ATG) treatment. A relapse after ATG was also seen in a patient exhibiting polyclonal hematopoiesis. Conversely, a monoclonal pattern did not preclude the occurrence of a partial or complete response to ATG. Other potential markers to study clonality, including cytogenetic abnormalities or point mutations of the N-ras protooncogene, were not found in any of the patients. It is concluded that patients with AA may exhibit clonal hematopoiesis. The significance with respect to evolution to disorders with clonal hematopoiesis like paroxysmal nocturnal hemoglobinuria, myelodysplasia, and acute leukemia remains to be determined.
Department of Hematology, University Medical Center, Leiden, The Netherlands.
H
H
van Kamp
J E
JE
Landegent
R P
RP
Jansen
R
R
Willemze
W E
WE
Fibbe
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000473:pathology*; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D015139:Blotting, Southern; D002999:Clone Cells / Q000473:pathology*; D004247:DNA / Q000032:analysis; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008214:Lymphocytes / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010735:Phosphoglycerate Kinase / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D013601:T-Lymphocytes / Q000276:immunology; D014960:X Chromosome
D000961:Antilymphocyte Serum; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; D010735:Phosphoglycerate Kinase