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

 

Prolonged lymphocytosis during Ibrutinib therapy

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has outstanding activity in patients with chronic lymphocytic leukemia. Most patients experience lymphocytosis, representing lymphocyte egress from nodal compartments.

This resolves within 8 months in the majority of patients, but a subgroup has lymphocytosis lasting >12 months. Here we report a detailed characterization of patients with persistent lymphocytosis during ibrutinib therapy. Signaling evaluation showed that while BTK is inhibited, downstream mediators of B-cell receptor (BCR) signaling are activated in persistent lymphocytes. These cells cannot be stimulated through the BCR and do not show evidence of target gene activation.

Progression-free survival is not inferior for patients with prolonged lymphocytosis vs those with traditional responses. Thus, prolonged lymphocytosis is common following ibrutinib treatment, likely represents the persistence of a quiescent clone, and does not predict a subgroup of patients likely to relapse early.

For more information: CLICK HERE

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.

For More Information: CLICK HERE

Monoclonal Antibodies Could Add Power to CLL Treatment

Andrew Schorr from Patient Power in partnership with the CLL Global Research Foundation interview Dr. Thomas Kipps, Director of the Blood Cancer Research Fund and the CLL Research Consortium about the use of rituximab, a monoclonal antibody used to treat patients with chronic lymphocytic leukemia

Clink here to watch the video now!

Developmental Protein Plays a Role in Spread of Cancer

http://health.ucsd.edu/news/releases/Pages/2013-06-14-developmental-protein-plays-cancer-role.aspx

Dr. Thomas Kipps and scientists from his research laboratory at the UC San Diego Moores Cancer Center discover an association between a protein called ROR1 and EMT, a process that occurs during embryogenesis.

Read the above article to learn more!

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

Ibrutinib, a potential breakthrough in treating chronic lymphocytic leukemia (CLL)

(TIME.com) — It’s called ibrutinib, and it’s a potential breakthrough in treating chronic lymphocytic leukemia (CLL) that could leave patients with fewer side effects than chemotherapy.   

 

Read the story from CNN:  Ibrutinib new hope for CLL Treatment

 

Power of Positive Thinking

Stay Positive!  Several questions about the power of a positive outlook have come into us here at the BCRF.  While we are not psychologist there are volumes of information and research into the importance of positive attitudes!  Click on the links below for just some of the information that is out there:

“The day is what you make it! So why not make it a great one?” ~ Steve Schulte

Can you make the train go in either direction? Try it! It is possible to make it go away and towards you!

You’re Going Down CLL!!!

New pieces to the puzzle are being identified in the Kipps’ BCRF lab:

(click to see article links)