The role of BCL11B in hematological malignancy

B-cell leukemia/lymphoma 11B (BCL11B) was first described by Ed Satterwhite in 2001. The BCL11B gene is located on mouse chromosome 12 (52.0？cM) and human chromosome 14 (q32.1). Murine BCL11B shows 88% identity to the human BCL11B at nucleotide level. It has been successfully demonstrated that BCL11B expression begins in the early double negative 1 (DN 1) cell stage in the thymus, and is primarily expressed in T cells, thymocytes and brain tissue [1]. This gene was originally referred to as RIT1 (radiation-induced tumor suppressor gene 1) because BCL11B was isolated by scanning γ-ray-induced mouse thymic lymphomas for the loss of specific chromosomal DNA [2]. BCL11B is also known as CTIP2 (COUP-TF-interacting protein 2) because it was isolated for its interaction with the orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor (COUP-TF) [3]. The BCL11B gene consists of 4 exons, and two alternatively spliced transcript variants, which encode distinct isoforms possessing or lacking exon 3, have been reported (Figure？ 1) [4,5].BCL11B belongs to the Kruppel-like C2H2 type zinc finger transcription factor family that contains 6 C2H2 zinc fingers and proline-rich and acidic regions with 95% identity in their zinc finger domains [4]. BCL11B encodes two different isoforms consisting of 823 and 894 aa in humans (Figure？ 1). These structures include DNA binding and protein interacting regions. The long exon 4 comprises the 6 zinc-finger domains, and the 2nd and 3rd domains are responsible for DNA binding. Apart from the DNA binding region, BCL11B possesses domains responsible for interaction with proteins and protein complexes [5].The specific functions of this gene have yet to be determined. The number of BCL11B functional studies have recently been on the rise.As a transcription factor, BCL11B may be a bi-functional transcriptional regulator that acts as a repressor and transactivator [6]. BCL11B interacts with COUP-TF [3] and nucleosome remodeling