Modulation of CD44 in acute lymphoblastic leukemia identifies functional and phenotypic differences of human B cell precursors

• Published in: European journal of haematology 2001-06, Vol.66 (6), p.377-382
• Main Authors: Zittermann, Sandra I., Achino, Bibiana I., Agriello, Evangelina E., Halperín, Nora, Ramhorst, Rosanna E., Fainboim, Leonardo
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - immunology; B-Lymphocytes - pathology; BCP-ALL; Biological and medical sciences; Biomarkers; CD44; Cell Culture Techniques; Cell Differentiation - immunology; Coculture Techniques; Hematologic and hematopoietic diseases; homing receptors; Humans; Hyaluronan Receptors - metabolism; Immunophenotyping; Interleukin-7 - pharmacology; Kinetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Stromal Cells
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1034/j.1600-0609.2001.066006377.x

: CD44 expression and other B cell markers were analyzed in 38 samples of B cell precursors (BCP) from patients with acute lymphoblastic leukemia (ALL). According to the expression of CD10 and CD44, we established the following five stages of BCP‐ALL phenotypes that may represent different forms of interaction between BCP‐ALL and bone marrow‐adherent cells: stage 1, CD19+, CD44bright, CD10−; stage 2, CD19+, CD44bright, CD10dim/bright; stage 3, CD19+, CD44dim, CD10bright, CD20−/+; stage 4, CD19+, CD44dim, CD10dim, CD20+; and stage 5, CD19+, CD44bright, CD10−, CD20+. Next, we analyzed the modulation of CD44 according to the expression of the different BCP‐ALL phenotypes by incubating the samples under different culture conditions, including addition of stromal cells and interleukin (IL)‐7. In culture, the samples in stages 1 and 2 maintained high expression of CD44 and re‐expressed this molecule when cultured after trypsin treatment, indicating ongoing synthesis of CD44. Similarly, the stage 3 samples cultured in the presence of stromal cells, IL‐7, or both also upregulated CD44 expression in culture. In contrast, the low expression of CD44 on the presumably more mature stage 4 samples was not modified by the addition of stromal cells or IL‐7 or when cultured after trypsin treatment, suggesting that those cells had arrested CD44 synthesis. We concluded that down‐modulation of CD44 occurred in association with differentiation to phenotype stages 3 and 4 and we hypothesized that this down‐modulation might be associated with the exit of BCP‐ALL from the bone marrow.