In the bone marrow, hematopoietic stem cells are essential for the formation of B-cells. The presence of particular cell surface markers and the arrangement of Ig gene segments are indicative of an orderly developmental process (Eibel et al., 2014). Defects in any stage of B-cell development and maturation lead to B-cell malignancies and autoimmune diseases (Wang et al., 2020). The hallmark of acute lymphoblastic leukemia involves the presence of immature lymphoblasts in the bone marrow, blood, and extramedullary regions (Phelan and Advani, 2018). Almost 75–85 % of ALL cases are of B-cell lineage. The genetic causes of B-cell ALL includes MLL (Mixed-lineage leukemia) gene rearrangements, hypodiploidy, hyperdiploidy, chromosomal translocations like ETV6-RUNX1 (25 %), TCF3-PBX1 (5 %), BCR-ABL1 (3 %), dysregulation in hematopoietic genes (ARID5B, CEBPE, GATA3, BMI1, CDKN2A), lymphoid signaling (PAX5, IKZF1, EBF1), tumor suppressor genes and transcriptional regulators (JAK, RAS, ERG) (Bhojwani et al., 2015, Bloom et al., 2020, Panuciak et al., 2023). In spite of all the recent advances in B-cell ALL treatment, 20 % of children and 70 % of adults show poor prognosis and therefore need identification of new therapeutic targets to increase event free survival rate (Yang et al., 2023).
Transcription factors are crucial in activating cell-specific gene expression. TAL1, also known as SCL (Stem Cell Leukemia), is a helix loop helix transcription factor and a master regulator of hematopoiesis (Ong et al., 2024). It forms homodimers and heterodimers that bind with specific DNA sequences. TAL1 has been found to inhibit the activity of E47/E2A and HEB. The E2A, along with other transcriptional regulators PAX5, Foxo1, and EBF1, orchestrate the development of B-cell lineages. Absence of the E2A gene not only impairs lymphoid development but also causes complete absence of B-cells (Miyazaki et al., 2020, Palamarchuk et al., 2006). TAL1 regulates several levels of hematopoiesis, especially hematopoietic stem cell development and differentiation of erythroid and megakaryocytes (Kuvardina et al., 2017, Sharma et al., 2023). It controls cell proliferation, apoptosis, cell cycle regulation, heme biosynthesis, and cytoskeletal organization (Kassouf et al., 2010). TAL1 is exclusively expressed in lymphoid, erythroid, and myeloid progenitor cells (Correia et al., 2016). Generally, lymphoid cells have reduced TAL1 expression as compared to myeloid cells. TAL1 and LYL1 both are required for normal erythropoiesis and B-cell development. Ectopic expression of TAL1 and c-Kit genes has been observed in mature B lymphocytes (Vagapova et al., 2018).
The current study was designed to ascertain whether BLACE expression may be utilized as a diagnostic biomarker in patients with B-cell acute lymphoblastic leukemia.
