BAALC, a novel marker of human hematopoietic progenitor cells

Abstract

Objective: The gene BAALC (Brain And Acute Leukemia, Cytoplasmic), a novel molecular marker involved in leukemia, is highly expressed in a subset of patients with acute leukemia and predictive of clinical outcome in patients with acute myeloid leukemia and normal karyotype. The role of BAALC in hematopoiesis and leukemogenesis is unknown.

Material and methods: We used real-time RT-PCR to show that BAALC is strongly expressed in CD34(+) cells from the bone marrow and blood and only weakly expressed in total normal bone marrow and blood cells.

Results: Expression analyses of FACSorted cells revealed high BAALC transcript levels in CD34(+) bone marrow cells including CD34(+)/CD38(-), CD34(+)/CD33(+), as well as CD34(+)/CD19(+)/CD10(+), CD34(+)/CD7(+), and CD34(+)/CD71(+)/CD45(-) cell fractions. Expression was significantly lower in all CD34(-) fractions. In vitro differentiation of CD34(+) bone marrow cells showed downregulation of BAALC and CD34 transcripts as early as day 4 in suspension cultures supplemented with lineage-specific cytokines (G-CSF, M-CSF, or EPO). In cultures with only lineage-unspecific cytokines (IL-3, SCF, GM-CSF), BAALC transcripts persisted up to day 20, while CD34 transcripts disappeared earlier. These observations suggest that expression of BAALC is stage specific.

Conclusions: BAALC expression is restricted to progenitor cells, and downregulation of BAALC occurs with cell differentiation. We postulate that BAALC represents a novel marker of an early progenitor cell common to the myeloid, lymphoid, and erythroid pathways.