Hot on the ROR1 t(r)ail

ROR1 can interact with TCL1 and enhance leukemogenesis in Eμ-TCL1 transgenic mice.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic antigen found on chronic lymphocytic leukemia (CLL) B cells, but not on normal adult tissues. We generated transgenic (Tg) mice with human ROR1 regulated by the murine Ig promoter/enhancer. In contrast to nontransgenic littermates, such animals had B-cell-restricted expression of ROR1 and could develop clonal expansions of ROR1(bright)CD5(+)B220(low) B cells resembling human CLL at ≥ 15 mo of age. Because immune-precipitation and mass spectrometry studies revealed that ROR1 could complex with T-cell leukemia 1 (TCL1) in CLL, we crossed these animals with Eµ-TCL1-Tg (TCL1) mice. Progeny with both transgenes (ROR1 × TCL1) developed CD5(+)B220(low) B-cell lymphocytosis and leukemia at a significantly younger median age than did littermates with either transgene alone. ROR1 × TCL1 leukemia B cells had higher levels of phospho-AKT than TCL1 leukemia cells and expressed high levels of human ROR1, which we also found complexed with TCL1.

Transcriptome analyses revealed that ROR1 × TCL1 leukemia cells had higher expression of subnetworks implicated in embryonic and tumor-cell proliferation, but lower expression of subnetworks involved in cell-cell adhesion or cell death than did TCL1 leukemia cells. ROR1 × TCL1 leukemia cells also had higher proportions of Ki-67-positive cells, lower proportions of cells undergoing spontaneous apoptosis, and produced more aggressive disease upon adoptive transfer than TCL1 leukemia cells. However, treatment with an anti-ROR1 mAb resulted in ROR1 down-modulation, reduced phospho-AKT, and impaired engraftment of ROR1 × TCL1 leukemia cells. Our data demonstrate that ROR1 accelerates development/progression of leukemia and may be targeted for therapy of patients with CLL.

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Stopping the Spread of Cancer

Stopping cancer’s spread: New protein found to control deadly cancer metastasis

Researchers have found a critical element that may explain why some cancers spread farther and faster than others, a discovery that could lead to one of the Holy Grails of cancer treatment: containing the disease.

Scientists from the University of California, San Diego School of Medicine, Dr. Thomas J. Kipps and colleagues,  have identified a protein that seems to serve as a switch, regulating the spread of cancer from the primary tumor to distant spots in the body – a process known as metastasis.  The protein is used by embryo cells during early development, but then disappears from the body after an individual comes out of the womb.

Read more- Fox News Report: Dr. Kipps

ROR1 Antibody

miR-125b and CLL

The downregulation of miR-125b in chronic lymphocytic leukemias leads to metabolic adaptation of cells to a transformed state.

MiR-125b-1 maps at 11q24, a chromosomal region close to the epicenter of 11q23 deletions in chronic lymphocytic leukemias (CLLs). Our results establish that both aggressive and indolent CLL patients show reduced expression of miR-125b. Overexpression of miR-125b in CLL-derived cell lines resulted in the repression of many transcripts encoding enzymes implicated in cell metabolism.