Bcl11a is essential for normal lymphoid development

Abstract

Bcl11a (also called Evi9) functions as a myeloid or B cell proto-oncogene in mice and humans, respectively. Here we show that Bcl11a is essential for postnatal development and normal lymphopoiesis. Bcl11a mutant embryos lack B cells and have alterations in several types of T cells. Phenotypic and expression studies show that Bcl11a functions upstream of the transcription factors Ebf1 and Pax5 in the B cell pathway. Transplantation studies show that these defects in Bcl11a mutant mice are intrinsic to fetal liver precursor cells. Mice transplanted with Bcl11a-deficient cells died from T cell leukemia derived from the host. Thus, Bcl11a may also function as a non-autonomous T cell tumor suppressor gene.

Somatic stem cells and the origin of cancer

“…In early stages, both PU.1 and Ikaros control the balance between myeloid or lymphoid commitment of MMPs through regulation of different signaling receptors (FLT3, c-KIT and IL-7R) [157][158][159] . More committed, earliest B cell progenitor transition to pro-B cell depends on addi-tional transcription factors (E2A, EBF, PAX5 and BCL11A), which coordinately activate appropriate Bcell expression programs and immunoglobulin heavychain gene rearrangements [160][161][162][163][164][165] . (fig.…”

Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11AXL protein are frequent in primary mediastinal B-cell lymphoma

“…3 Furthermore, retroviral integration to the BCL11A locus has been shown to activate its expression, transform NIH 3T3 cells and induce myeloid leukemias in mice. 4 In the Burkitt's lymphoma cell line NAB-2, the EpsteinBarr virus (EBV) is integrated in the BCL11A locus leading to slightly higher BCL11A expression compared to other EBVpositive as well as EBV-negative Burkitt's lymphoma-derived cell lines. 5 Thus, deregulated expression of BCL11A through either genomic amplification, chromosomal translocation or abnormal activation (e.g., upon viral integration) is suggested to play a role in lymphomagenesis.…”

The BCL11AXL transcription factor: its distribution in normal and malignant tissues and use as a marker for plasmacytoid dendritic cells

“…1 BCL11A encodes a Krü ppel zinc-finger transcription factor, and Evi9/Bcl11a/Ctip1 (mouse homologue of human BCL11A) has been shown to be essential for pre-B-cell development and thymocyte maturation. 2 There is evidence that Bcl11a, and hence human BCL11A, may not only encode a dominant proto-oncogene but also function as a non-autonomous T-cell tumor suppressor gene. 2 Alternative RNA splicing generates at least three BCL11A transcripts with restricted expression in bone marrow, lymphoid tissue and brain.…”

“…2 There is evidence that Bcl11a, and hence human BCL11A, may not only encode a dominant proto-oncogene but also function as a non-autonomous T-cell tumor suppressor gene. 2 Alternative RNA splicing generates at least three BCL11A transcripts with restricted expression in bone marrow, lymphoid tissue and brain. BCL11A XL mRNA is the largest and the most abundant transcript.…”

“…7 BCL11A XL was detected in the T-ALL-derived Jurkat, MKB1 and CEM T-cell lines and a small subpopulation of the myeloid U937 cells. Liu et al 2 reported Bcl11A expression to be important not only for B-cell differentiation but also for T-cell maturation and the development of T-cell leukemia. The presence of BCL11A XL protein in normal and malignant T cells is therefore not inconsistent with these findings.…”