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.
Zittermann
S I
SI
Laboratory of Immunogenetics, Hospital de Clínicas, School of Medicine, University of Buenos Aires, Argentina.
Achino
B I
BI
Agriello
E E
EE
Halperín
N
N
Ramhorst
R E
RE
Fainboim
L
L
D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D015415:Biomarkers; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000494:pharmacology; D007700:Kinetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D017154:Stromal Cells
D015415:Biomarkers; D018960:Hyaluronan Receptors; D015851:Interleukin-7