Mechanisms of transcription factor deregulation in lymphoid cell transformation

Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia

“…For this reason the genetic instability has been postulated to be one of the hallmarks of cancer (16). Genetic alterations in ALL (Table 3) include structural or numerical chromosome changes such as translocations or hyperdiploidy (17), deletions and amplifications (15,18).…”

“…Some genetic alterations affect only one of these pathways, whereas others act on more than one (2) (17,18) . However, the detection of chromosomal translocations in healthy donors and experiments in transgenic mice indicate that a single chromosomal translocation is not enough to induce leukemia, depending on the translocation investigated.…”

“…For example, the t(11;10), t(11;19) fuse MLL to AF-9 and ENL, respectively. These two partners are small serine/proline-rich proteins with nuclear localization signals, suggesting that they may function as transcriptional transactivators (18). The MLL protein is a nuclear protein that maintains the expression of particular members of the HOX family.…”

Genomic tools for dissecting oncogenic transcriptional networks in human leukemia

“…T-ALL transcription factor oncogenes include members of the bHLH family, such as TAL1, TAL2, LYL1, BHLHB1 and MYC; the LIM-only domain (LMO) genes LMO1 and LMO2; the orphan homeobox genes TLX1/HOX11 and TLX2/HOX11L2, members of the HOXA gene paralog group, including HOXA9 and HOXA10; MYB, and most prominently, the frequently mutated NOTCH1 gene. 2,56,57 The TAL1 gene in chromosome band 1p32 plays an essential role in the generation of early hematopoietic progenitors and in the development of erythroid and megakaryocytic cell lineages. 58 Aberrant expression of TAL1 is present in over 60% of T-ALL cases 2,59 and its oncogenic potential is illustrated by the induction of T-cell lymphoblastic tumors in transgenic mice.…”

Aberrant DNA Methylation and Epigenetic Inactivation of hMSH2 Decrease Overall Survival of Acute Lymphoblastic Leukemia Patients via Modulating Cell Cycle and Apoptosis

“…The deficiencies of MMR genes are also associated with MNNG, 6-thioguanine and cisplatin (Fiumicino et al, 2000;Meyers et al, 2001;Loo et al, 2005). Altered expression of key regulatory transcription factors has been shown to play a critical role in the leukemia development (O'Neil and Look, 2007). Molecular biological studies have shown that hMSH2 may be functionally relevant in the lymphoid cells and potentially ALL.…”