Understanding ROR1

ROR1, an oncogene recently discovered on chronic lymphocytic leukemia (CLL) B cells, is being studied by researchers as a potential target for CLL treatment. Dr. Brian Koffman met with Dr. Thomas Kipps, who is researching ROR1, at the 2014 American Society of Clinical Oncology (ASCO) meeting to discuss this oncogene and its potential use in treating CLL.

Click HERE: https://www.youtube.com/watch?v=Zji6Fux_WGo

Thanks to Patient Power!fig1

 

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

4/6/2013 Fighting Cancer at the UC San Diego Moores Cancer Center

In an article published in the San Diego Union Tribune,  assistant project scientist, Emanuela Ghia, PhD, is highlighted at the Moores UC San Diego Cancer Center fight against cancer in association with the American Cancer Society.  While this article focuses on breast cancer research, it highlights some of the important advances, applications, and techniques that we are applying in our fight against CLL and other blood cancers.

To read the full article click on the link below:

Genetics Seen as Key to Cancer Fight

Subclonal evolution involving SF3B1 mutations in chronic lymphocytic leukemia

In this report, Dr. Schwaederlé and other research associates at the UC San Diego BCRF lab investigate the progression of SF3B1 mutations in the CLL B cells over time in an attempt to elucidate whether there exists subclonal evolution involving SF3B1 mutations in CLL. Accumulation of CLL cells harboring mutations in SF3B1 suggests that such subclones have some competitive advantage, which might account for accelerated progression of the disease in some patients over time. Alternatively, subclones of CLL cells might be selected during therapy, similar to what has been observed in mutations involving TP53 in CLL cells of patients treated with standard chemotherapy.

Click Here to see the full article