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CD66c antigen expression is myeloid restricted in normal bone marrow but is a common feature of CD10+ early-B-cell
P Boccuni1, R Di Noto, C Lo Pardo
1Divisione di Ematologia, Università Frederico II, Napoli, Italy.
Insights
CD66c expression is myeloid-restricted in normal bone marrow but found on some acute myeloid leukemias and most CD10+ early B-acute lymphoblastic leukemias. This aids in distinguishing leukemic cells from normal regenerating cells.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- CD66c is a cell surface molecule with known expression on peripheral granulocytes.
- Its role in early hematopoiesis, both normal and neoplastic, requires further elucidation.
Purpose of the Study:
- To investigate the expression profile of CD66c in normal bone marrow and various hematologic malignancies.
- To assess the utility of CD66c as a marker in diagnosing and monitoring leukemias.
Main Methods:
- Flow cytometry was employed to analyze CD66c cell surface expression.
- Samples included bone marrow from healthy subjects and patients with de novo acute myeloid leukemia (AML), blastic phases of chronic myelogenous leukemia, acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphomas.
- Dual staining with CD66c and CD10 was utilized for specific patient subgroups.
Main Results:
- In normal bone marrow, CD66c expression was restricted to myeloid cells, peaking at the promyelocyte stage.
- Slight CD66c expression was observed in a subset of AML-M4 and rarely in other AML subtypes. Acute promyelocytic leukemia (APL) cases predominantly lacked CD66c, but expression was induced by all-trans retinoic acid.
- CD10+ early B-acute lymphoblastic leukemia (B-ALL) consistently expressed CD66c (87%), while CD10- early B-ALL and SmIg+ B-ALL lacked it.
- Dual CD66c/CD10 staining effectively differentiated residual CD10+/CD66c+ leukemic cells from normal CD10+/CD66c- regenerating B cells in CD10+ early-B-ALL.
Conclusions:
- CD66c exhibits a distinct expression pattern in normal and malignant hematopoiesis.
- CD66c serves as a potential diagnostic marker in specific leukemic subtypes, particularly CD10+ early B-ALL.
- CD66c, in conjunction with CD10, offers a valuable tool for monitoring minimal residual disease in CD10+ early-B-ALL.
Abstract:
CD66c is a surface (and intracellular) molecule bound to the membrane by a glycosyl-phosphatidylinositol anchor. While its expression on peripheral granulocytes is well recognized, less is known about its distribution in early steps of normal and neoplastic hematopoiesis. We analyzed by flow cytometry cell surface expression of CD66c on bone marrow cells from 4 healthy subjects and on bone marrow or peripheral blood cells from 127 patients with newly diagnosed hematologic malignancies: 70 de novo acute myeloid leukemias (AML), 6 refractory anemias with excess of blasts in transformation, 3 myeloid and 3 lymphoid blastic phases of chronic myelogenous leukemia, 33 B-lineage and 6 T-lineage acute lymphoblastic leukemias (B- and T-ALL), and 3 B-cell and 3 T-cell non-Hodgkin's lymphomas in the leukemic phase. We found that in normal bone marrow CD66c expression was myeloid restricted, reaching its highest level on promyelocytes. As for de novo AML, slight expression of CD66c was found on 6/25 (24%) AML-M4 and only occasionally in other subgroups. In 9 out of 10 cases of acute promyelocytic leukemia, CD66c was totally absent, but antigen expression was easily detectable following in vitro exposure to all-trans retinoic acid. Among lymphoid malignancies, CD10+ early-B-ALL consistently expressed the molecule (20/23 cases, or 87%) whereas both CD10- early-B ALL and SmIg+ B-ALL completely lacked it. Finally, dual staining with CD66c and CD10 proved to be a suitable tool for distinguishing even low percentages of residual leukemic cells (CD10+/CD66c+) from normal regenerating early-B cells (CD10+/CD66c ) in CD10+ early-B-ALL induced into remission.