Abstract
B cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent type of cancer in children. Despite progresses in curative treatment, intensive chemotherapy regimens still cause life threatening complications. A better understanding of the molecular mechanisms underlying the emergence and maintenance of BCP-ALL is fundamental for the development of novel therapies. Here, we establish that SOX7 is frequently and specifically expressed in BCP-ALL and that the expression of this transcription factor does not correlate with any specific cytogenetic abnormalities. Using human leukemia model systems, we establish that the down-regulation of SOX7 in BCP-ALL causes a significant decrease in proliferation and clonogenicity in vitro that correlates with a delay in leukemia initiation and burden in vivo. Overall, these results identify a novel and important functional role for the transcription factor SOX7 in promoting the maintenance of BCP-ALL.
Highlights
Acute lymphoblastic leukemia (ALL) is the most frequent type of cancer in children and comprises neoplastic precursor cells committed to the B cell (BCPALL) or the T cell (T-ALL) lineages
This analysis revealed that SOX7 expression levels were frequently and significantly higher in childhood and adult B cell precursor acute lymphoblastic leukemia (BCP-ALL) when compared to normal bone marrow and other types of leukemia, including T-Cell Acute Lymphoblastic Leukemia (T-ALL), acute myeloid leukemia (AML), chronic leukemias and myelodysplastic syndrome (MDS) (Figure 1A and S1A–S1B)
These results establish that the transcription factor SOX7 is and frequently expressed in human BCP-ALL, without an obvious association with specific chromosomal abnormalities or cytogenetic subtypes
Summary
Acute lymphoblastic leukemia (ALL) is the most frequent type of cancer in children and comprises neoplastic precursor cells committed to the B cell (BCPALL) or the T cell (T-ALL) lineages. BCP-ALL represents the majority of ALL, accounting for up to 85% of childhood ALL and 75% of adult ALL [1]. Genes involved in B cell development such as EBF1, IKZF1, PAX5 or PBX1 are frequently found mutated in BCP-ALL [2, 3]. While childhood BCP-ALL is curable in most cases with a survival rate approaching 80%, the rate of cure for adult patients presenting with BCP-ALL is only 40% [4, 5]. Despite progresses in the treatment of BCP-ALL, intensive chemotherapy regimens cause life threatening complication and around 20% of the treated patients relapse presenting a very poor outcome [6]. There is a great need for the development of less toxic compounds and novel therapies for the treatment of relapsed and specific subgroups of BCP-ALL patients with poor prognosis
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