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This Week in Cancer Cell: Jul 22, 2011


In Cancer Cell this week, researchers in New York and Chicago write that somatic loss-of-function mutations in the ten-eleven translocation 2 gene can lead to increased hematopoietic stem cell self-renewal and myeloid transformation. The Tet2 mutations occur in many patients with myeloid malignancies, the authors add. In this study, the team found that Tet2 loss leads to a "progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo." In addition, the team saw that Tet2+/- mice displayed increased stem cell self-renewal and extramedullary hematopoiesis.

Also in Cancer Cell this week, Massachusetts researchers report their method for the selective killing of mixed lineage leukemia cells using a potent, small-molecule DOT1L inhibitor. Mislocated enzymatic activity of DOT1L has been suggested as a possible driver of leukemogenesis in mixed lineage leukemia, the authors write. Treatment of MLL cells with a compound called EPZ004777 — a selective inhibitor of DOT1L — resulted in the compound "selectively inhibit[ing] H3K79 methylation and block[ing] expression of leukemogenic genes," the team adds. Exposure to EPZ004777 results in selective killing of those specific cells that carry the MLL gene translocation, with little to no effect on normal cells. In vivo administration of the compound in mice MLL xenograft models increased survival rates in sick mice, the researchers write.

And finally in Cancer Cell this week, researchers in the US and Europe suggest that an "axis" between Pin1 and mutant p53 promotes aggressiveness in breast cancer. Pin1 enhances tumorigenesis in a mouse model and cooperates with mutant p53 in Ras-dependent transformation, the authors write. In breast cancer, Pin1 promotes mutant p53 dependent inhibition of the antimetastatic factor p63, and induces a mutant p53 transcriptional program to increase the aggressiveness of the tumor. "In a cohort of patients, Pin1 overexpression influenced the prognostic value of p53 mutation," the team adds. "These results define a Pin1/mutant p53 axis that conveys oncogenic signals to promote aggressiveness in human cancers."

The Scan

US Booster Eligibility Decision

The US CDC director recommends that people at high risk of developing COVID-19 due to their jobs also be eligible for COVID-19 boosters, in addition to those 65 years old and older or with underlying medical conditions.

Arizona Bill Before Judge

The Arizona Daily Star reports that a judge is weighing whether a new Arizona law restricting abortion due to genetic conditions is a ban or a restriction.

Additional Genes

Wales is rolling out new genetic testing service for cancer patients, according to BBC News.

Science Papers Examine State of Human Genomic Research, Single-Cell Protein Quantification

In Science this week: a number of editorials and policy reports discuss advances in human genomic research, and more.