SALL4 is a key regulator of survival and apoptosis in human leukemic cells

Abstract

Increasing studies suggest that SALL4 may play vital roles in leukemogenesis and stem cell phenotypes. We have mapped the global gene targets of SALL4 using chromatin immunoprecipitation followed by microarray hybridization and identified more than 2000 highconfidence, SALL4-binding genes in the human acute promyelocytic leukemic cell line, NB4. Analysis of SALL4-binding sites reveals that genes involved in cell death, cancer, DNA replication/repair, and cell cycle were highly enriched (P < .05).These genes include 38 important apoptosis-inducing genes (TNF, TP53, PTEN, CARD9, CARD11, CYCS, LTA) and apoptosis-inhibiting genes (Bmi-1, BCL2, XIAP, DAD1, TEGT). Real-time polymerase chain reaction has shown that expression levels of these genes changed significantly after SALL4 knockdown, which ubiquitously led to cell apoptosis.

Stem Cell Gene SALL4 Suppresses Transcription through Recruitment of DNA Methyltransferases

“…4d). This result is consistent with our previous work from leukemia cell line as well as data obtained from leukemic bone marrow of SALL4B transgenic mice, in which PTEN expression was also suppressed (14,21).…”

“…We next sought further evidence of SALL4-mediated DNA methylation modifications in human leukemia cells (NB4), in which SALL4 functions as a critical survival factor by suppressing PTEN expression (21). For this purpose, cells were transduced with GFP control or SALL4-expressing lentiviruses as described under "Experimental Procedures" and in Ref.…”

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

“…51,52 Morphologically, metastatic yolk sac tumor or other germ cell tumors should be easily distinguished from these entities. In difficult cases, an immunohistochemical panel including antibodies toward CD10, CD19, CD79a, and TDT for precursor B lymphoblastic lymphoma and myeloperoxidase, leukocyte common antigen (CD45), CD43, and CD34 for myeloid leukemia should help in making the distinction from germ cell tumor.…”

Targeting the translational apparatus to improve leukemia therapy: roles of the PI3K/PTEN/Akt/mTOR pathway

“…The SALL4 transcription factor is involved in the maintenance of pluripotency and self-renewal of embryonic stem cells. [44][45][46] There are numerous transcription factors that bind the PTEN promoter region to regulate transcription. Various transcription factors can have positive (for example, Egr-1, Atf2, p53, CBP/p300, PPARg, CBF-1) or negative effects (for example, nuclear factor kappa from B cells, Snail1, Bmi-1, c-Jun, p53, PPARg, CBF-1) on PTEN transcription.…”