HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24.

Kennedy, Martin A.; González‐Sarmiento, Rogelio; Kees, Ursula R.; Lampert, F.; Dear, Neil; Boehm, Thomas; Rabbitts, Terence H.

doi:10.1073/pnas.88.20.8900

Cited by 229 publications

(138 citation statements)

References 40 publications

Supporting

Mentioning

136

Contrasting

Order By: Relevance

“…8 A recent analysis of 10 HOX11L2-positive of 81 adult T-ALL patients found HOX11L2 expression to be associated with induction therapy failure, failure to respond to a salvage regimen as well as a higher relapse rate and reduced OS. 20 Due to the large number of subjects in our study we are able to show an independent negative prognostic impact of HOX11L2 expression by multivariate analysis. Also, we are able to confirm the immunophenotype as strong prognostic factor for RFS as well as OS.…”

Section: Hox11l2-positive Thymic T-all With Reduced Outcomementioning

confidence: 61%

Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group

et al. 2008

View full text Add to dashboard Cite

Adult T-cell acute lymphoblastic leukemia (T-ALL) continues to represent an unfavorable disease. Molecularly based treatment stratifications could help improve outcome. The prognostic impact of HOX11 and HOX11L2 expression has been an area of controversy. We have investigated 286 adult T-ALL patients enrolled into the German Multicenter ALL (GMALL) therapy protocols by comparative real-time RT-PCR. High HOX11 expression and HOX11L2 expression were predominantly seen in thymic T-ALL (P ¼ 0.031). In a multivariate analysis HOX11L2 expression proved to be an independent adverse risk factor for relapse-free survival (RFS) with a hazard ratio (HR) of 2.02 (P ¼ 0.023) and an HR for overall survival (OS) of 1.81 (P ¼ 0.021), both adjusted for the immunophenotype. HOX11 expression was found to have a favorable impact on RFS (HR 0.51; P ¼ 0.048) but did not exhibit a significant impact on OS. A subgroup analysis for thymic T-ALL revealed a more pronounced negative correlation of HOX11L2 expression with RFS (HR 3.26; P ¼ 0.002) and OS (HR 2.38; P ¼ 0.009). Although the prognostic impact of HOX11 in T-ALL is less clear, HOX11L2 expression identifies a small subset of high-risk patients, who are so far classified as standard-risk group. Thus, patients with aberrant HOX11L2 expression should be considered early as candidates for intensified treatment regimes.

show abstract

Section: Hox11l2-positive Thymic T-all With Reduced Outcomementioning

confidence: 61%

Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Recently, it was found that the homeobox protein HOX11 can bind and likely inhibit PP2A, resulting in the disruption of a G2/M cell-cycle checkpoint in both Xenopus oocytes and a human T-cell line (51). This alteration of the regulation of the cell cycle may be instrumental in the development of human T-cell leukemias that result from translocations that fuse the T-cell receptor ␣-or ␤-chain genes with the HOX11 gene (52,53). An important question is whether HRX fusion proteins together with SET perform a function similar to HOX11 in overcoming a G2/M cell cycle checkpoint.…”

Section: Discussionmentioning

confidence: 99%

HRX Leukemic Fusion Proteins Form a Heterocomplex with the Leukemia-associated Protein SET and Protein Phosphatase 2A

Adler

Nallaseth

Walter

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

One of the most common chromosomal abnormalities in acute leukemia is a reciprocal translocation involving the HRX gene at chromosome locus 11q23, resulting in HRX fusion proteins. Using the yeast two-hybrid system, in vitro binding studies, and human cell culture coimmunoprecipitation experiments, we show here that a region of the HRX protein that is consistently retained in HRX leukemic fusion proteins interacts directly with SET, another protein implicated in leukemia. We have identified the binding sites on HRX for SET and show that these sequences are clustered near the A⅐T hooks that have been shown to bind DNA. We also show that carboxyl-terminal SET sequences, possibly the acidic tail of SET, bind to HRX. We have also found serine/ threonine-specific protein phosphatase activity in anti-HRX coimmunoprecipitates. Using the phosphatase inhibitor okadaic acid and Western blotting, the phosphatase was identified as protein phosphatase 2A (PP2A). Mutation of a single amino acid in one of the SET binding sites of HRX resulted in lower amounts of both coimmunoprecipitated SET protein and coimmunoprecipitated PP2A. These results suggest that the leukemogenic effects of HRX fusion proteins may be related to interactions with SET and PP2A.

show abstract

“…Patients were diagnosed and treated at the Princess Margaret Hospital for Children, Perth, Western Australia, and informed consent was obtained from parents, patients, or both as deemed appropriate. Several of the cell lines have been described previously (Kees, 1987;Kees et al, 1987Kees et al, , 1989aKees et al, , b, 1990Kees et al, , 1995Kees et al, , 2003Kennedy et al, 1991;Whitman et al, 2001). CCRF-HSB2 (HSB2) cells were obtained from the American Type Culture Collection; CCRF-CEM (CEM) from the Children's Cancer Institute Australia for Medical Research, Sydney; JURKAT from the Basel Institute for Immunology, Switzerland; ALL-SIL from MRC Laboratory of Molecular Biology, Cambridge, UK; MOLT4 from the German Cancer Research Center, Heidelberg, Germany; DU.528 from the Division of Cancer Biology, Telethon Institute for Child Health Research, Perth.…”

Section: Cell Linesmentioning

confidence: 99%

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

et al. 2006

Self Cite

View full text Add to dashboard Cite

Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53 -442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC 50 48000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.

show abstract

HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24.

Cited by 229 publications

References 40 publications

Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group

Thymic adult T-cell acute lymphoblastic leukemia stratified in standard- and high-risk group by aberrant HOX11L2 expression: experience of the German multicenter ALL study group

HRX Leukemic Fusion Proteins Form a Heterocomplex with the Leukemia-associated Protein SET and Protein Phosphatase 2A

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

Contact Info

Product

Resources

About