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

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.