title: CD44 and CD27 delineate B-precursor stages with different recombination status and with an uneven distribution in nonmalignant and malignant hematopoiesis.
abstract: The expression of CD27 and CD44 correlate with the genotype of B-precursor acute lymphoblastic leukemia (ALL). Based on the expression of these antigens, we identified counterparts of TEL/AML1(pos) and TEL/AML1(neg) leukemic cells in nonmalignant bone marrow. Although CD27 is known as a marker of mature memory B cells, we recently showed that CD27 is also expressed by malignant and nonmalignant B precursors. Here, we show that CD27 and CD44 delineate stages of B-precursor development. Well-established differentiation markers showed that the developmental sequence starts from undetermined progenitors, expressing CD44. Upon B-lineage commitment, cells gain CD27 and lose CD44. The CD27(pos)CD44(neg) (CD27 single positive, 27SP) cells are the earliest stage within CD10(pos)CD19(pos) B precursors and express RAG-1 and TDT. These cells correspond to TEL/AML1(pos) ALL (1/4 pediatric B-precursor ALL). The development follows to CD27/CD44 double-positive (27/44DP) stage, 44SP stage and CD27/CD44 double-negative (27/44DN) stage. Before exit to periphery, CD44 is reexpressed. The 27/44DP cells are mostly large and profoundly suppress RAG-1. Despite their presumably high proliferation potential, 27/44DP cells rarely dominate in leukemia. At 44SP stage, which corresponds to TEL/AML1(neg) leukemias, RAG-1 is reexpressed and Ig light chain gene starts to be rearranged.
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Medical School, Charles University Prague, Prague, Czech Republic. martina.vaskova@lfmotol.cuni.cz
authors.forename: M
authors.initials: M
authors.lastname: Vaskova
authors.forename: E
authors.initials: E
authors.lastname: Fronkova
authors.forename: J
authors.initials: J
authors.lastname: Starkova
authors.forename: T
authors.initials: T
authors.lastname: Kalina
authors.forename: E
authors.initials: E
authors.lastname: Mejstrikova
authors.forename: O
authors.initials: O
authors.lastname: Hrusak
mesh_terms: D002648:Child; D018507:Gene Expression Regulation, Developmental; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016130:Immunophenotyping; D015448:Leukemia, B-Cell / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology*; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D018960:Hyaluronan Receptors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7