E-GEOD-47421 - Ectopic Expression data of TLX1 in Hematopoietic Progenitors in TLX1 Transgenic Mice Deficient in DNA-PK
Released on 5 April 2014, last updated on 3 June 2014
The noncluster homeodomain containing gene, HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell Acute Lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHµ-TLX1Tg mice, which developed mature B cell lymphoma after a long latency period suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHµ-TLX1Tg mice with PrkdcScid/Scid mice; To identify the molecular pathways dysregulated in the earliest stages of TLX1-induced transformation, we used Affimetrix microarrays to compare gene expression profiling of premaliganant thymocytes (6~8 weeks old): DN1, DN2 and DN3 stages from HOX11 transgenic PrkdcScid/Scid (HOXSCID) mice with the same stage thymocytes from the sex and age matched control PrkdcScid/Scid (SCID) mice. Expression analysis of IgH-TLX1TgPrkdcScid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic, mitotic spindle and anaphase-promoting complex genes in double negative (DN) 2 and DN3 stage thymocytes. Moreover, DN1, DN2 and DN3 TLX1-expressing thymocytes showed downregulated expression of ribosomal and mitochondria ribosomal protein genes. Four groups of double mutant IgH-HOX11TgPrkdcScid/Scid mice and four groups of control PrkdcScid/Scid mice were sacrificed at the age of 6~8 weeks and the fresh thymocytes were FACS sorted by markers CD25 and CD44 to DN1, DN2 and DN3 stages. To minimize the sample variability caused by individual differences among animals, about 2 ~5 the same phenotype, stage and sex thymocytes were pooled (total 104 ~ 105 cells) and used as one sample each for RNA extraction and hybridization on Affymetrix microarrays.
transcription profiling by array
Yan Zhen Zheng <firstname.lastname@example.org>, Edwin Chen, Konstantin Krutikov, Margaret R Hough, Yanzhen Zheng
Ectopic TLX1 Expression Accelerates Malignancies in Mice Deficient in DNA-PK. Krutikov K, Zheng Y, Chesney A, Huang X, Vaags AK, Evdokimova V, Hough MR, Chen E. , Europe PMC 24586935