Abstract
Phosphatase of regenerating liver-3 (PRL-3/PTP4A3) is upregulated in multiple cancers, including BCR-ABL1- and ETV6-RUNX-positive acute lymphoblastic leukemia (ALL). With this study, we aim to characterize the biological role of PRL-3 in B cell ALL (B-ALL). Here, we demonstrate that PRL-3 expression at mRNA and protein level was higher in B-ALL cells than in normal cells, as measured by qRT-PCR or flow cytometry. Further, we demonstrate that inhibition of PRL-3 using shRNA or a small molecular inhibitor reduced cell migration towards an SDF-1α gradient in the preB-ALL cell lines Reh and MHH-CALL-4. Knockdown of PRL-3 also reduced cell adhesion towards fibronectin in Reh cells. Mechanistically, PRL-3 mediated SDF-1α stimulated calcium release, and activated focal adhesion kinase (FAK) and Src, important effectors of migration and adhesion. Finally, PRL-3 expression made Reh cells more resistance to cytarabine treatment. In conclusion, the expression level of PRL-3 was higher in B-ALL cells than in normal cells. PRL-3 promoted adhesion, migration and resistance to cytarabine. PRL-3 may represent a novel target in the treatment of B-ALL.
Highlights
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, accounting for approximately one third of pediatric cancers
We demonstrate that PRL-3 expression at mRNA and protein level was higher in B-acute lymphoblastic leukemia (ALL) cells than in normal cells, as measured by quantitative real time PCR (qRT-PCR) or flow cytometry
PRL-3 expression was significantly higher in B cell ALL (B-ALL) samples than in normal samples in all three datasets (Figure 1C and Table 1)
Summary
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, accounting for approximately one third of pediatric cancers. Adhesion to bone marrow (BM) stroma and BM niches is vital for both normal and leukemic B-progenitor cells [3, 4]. Adhesion enables the cells to receive growth and survival signals, either through integrin-mediated signaling or through stimulation by interleukin (IL)-7 and other cytokines in the bone marrow microenvironment [7]. Cell www.impactjournals.com/oncotarget adhesion in the BM promotes resistance to chemotherapy [5, 6]. This cell adhesion-mediated drug resistance (CAMDR) has been considered a cause of minimal residual disease (MRD) and relapse of ALL [6]
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