Immunophenotype and clinical characteristics of CD45-negative and CD45-positive childhood acute lymphoblastic leukemia.
To evaluate the expression pattern of the leukocyte common antigen CD45 in acute leukemias and to investigate whether the lack of CD45 expression in childhood acute lymphoblastic leukemia (ALL) is associated with other immunophenotypic features and a distinct clinical behavior, we have carried out extensive immunophenotypic analyses of bone marrow and peripheral blood samples from 638 patients with childhood B-cell precursor (n=529) or T-lineage ALL (n=109). All 638 patients were enrolled in the German ALL-BFM 90 and ALL-BFM 95 trials. CD45 was detected on the surface of childhood ALL cells (cut-off > or = 20% positive cells) in only 88.7% (n=566) of all cases. Among 529 patients with childhood B-cell precursor ALL, 12.9% (n=68) did not express CD45, compared with only 3.7% (n=4) of patients with childhood T-lineage ALL (p < 0.001). In the B-cell precursor ALL subtypes, the highest frequency of CD45- cases (15.1%) was observed in common ALL (56/372) compared with only 7.2% in pro-B ALL (3/41) and 7.8% in pre-B ALL (9/116). Assessment of clinical parameters (age, organ enlargement, WBC, etc.) and event-free survival did not reveal significant differences between CD45- and CD45+ patients. Myeloid antigen coexpression was not correlated with CD45 expression. The mean percentage of antigen expression for CD34, CD10, TdT, CD22, and CD24 was significantly higher in children with CD45- B-cell precursor ALL than in those with CD45+ B-cell precursor ALL. In 28 patients with B-cell precursor ALL, cell cycle analyses of freshly isolated leukemic cells were performed with propidium iodide (PI) staining and flow-cytometric analysis. The percentage of cells in S-phase was inversely correlated to the percentage of CD45+ cells (r=-0.48, p < 0.05). With two-parameter analysis of CD45-fluorescein isothiocyanate (FITC)- and PI-stained cells in nine patients with a percentage of CD45+ cells between 40 and 60%, two populations were distinguishable in a single patient. It was shown that the CD45- subpopulation had a higher percentage of cells in S-phase than the CD45+ subpopulation (10.7 +/- 4.0 vs. 2.7 +/- 1.8, p < 0.007). We conclude that the lack of CD45 expression contributes to the identification of a distinct functional and immunological subgroup of B-cell precursor ALL, but that it has no significant impact on clinical behavior or on therapy outcome in childhood ALL.
Ratei
R
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Department of Hematology, Oncology and Tumor Immunology, Robert-Rössle-Klinik, Charité Campus Berlin-Buch, Humboldt University of Berlin, Germany. ratei@rrk-berlin.de
Sperling
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Karawajew
L
L
Schott
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Schrappe
M
M
Harbott
J
J
Riehm
H
H
Ludwig
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D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D019070:Cell Lineage; D002648:Child; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D017493:Leukocyte Common Antigens / Q000097:blood*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000276:immunology*; D011241:Prednisone / Q000627:therapeutic use; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D004273:DNA, Neoplasm; D017493:Leukocyte Common Antigens; D011241:Prednisone