Could sticky cells cause drug resistance in chronic blood cancer?

March 11, 2014
Could sticky cells cause drug resistance in chronic blood cancer?

(Medical Xpress)—Chronic myeloid leukaemia (CML) is associated with a specific genetic mutation that results from DNA on different chromosomes breaking off and swapping places. This disrupts genes at the breakpoint and the rejoining point. One of these disrupted genes is called BCR-ABL and drugs that target this mutation have transformed the treatment of CML. However, patients can develop resistance to these drugs, which causes their cancer to return.

Now scientists from The University of Manchester – part of the Manchester Cancer Research Centre - have measured the levels of the BCR-ABL genetic mutation in a cell model of CML. In particular, they separated into those that stuck to plastic – "sticky", or adherent, cells – and those non-adherent ones that did not, and looked for differences between the two groups of cells.

Dr Richard Byers, who jointly led the research, said: "Previous studies have linked high levels of the BCR-ABL mutation with drug resistance. We wanted to see how expression of BCR-ABL differed across groups of CML cells, and in particular whether there were differences between adherent and non-adherent populations."

In a study recently published in the journal Experimental Haematology, the group demonstrate that is wide variation in BCR-ABL expression levels in the cell model and the stickier cells have a higher level of BCR-ABL expression. These stickier cells were less sensitive to treatment with a BCR-ABL targeted drug, imatinib.

Dr Byers said: "The small number of cells that show high levels of BCR-ABL may not be detectable through bulk analysis of large samples. 

"It looks like it is important to look at protein levels in single cells. In future, it may be possible to measure BCR-ABL levels in in the clinic – this will help us identify the resistant high BCR-ABL cells and better understand how patients develop resistance to imatinib treatment with the aim of combatting this to make response more durable and the more effective."

Explore further: Researcher investigate 2-drug synergy to treat drug-resistant chronic myeloid leukemia

More information: Ehsan Ghayoor Karimiani, Fiona Marriage, Anita J. Merritt, John Burthem, Richard John Byers, Philip J.R. Day, "Single-cell analysis of K562 cells: An imatinib-resistant subpopulation is adherent and has upregulated expression of BCR-ABL mRNA and protein," Experimental Hematology, Available online 20 November 2013, ISSN 0301-472X, dx.doi.org/10.1016/j.exphem.2013.11.006.

Related Stories

Anchoring ABL for a better fate

August 27, 2013

Chronic Myelogenous Leukemia (CML) is a cancer of the white blood cells that is most commonly found in adults and in the elderly. Its incidence has been estimated to be 1 to 2 in 100,000 people. CML was the first cancer to ...

Ponatinib active in CML, ph+ acute lymphoblastic leukemia

November 5, 2013

(HealthDay)—Ponatinib is active in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), according to a study published online Nov. 1 in the New England Journal ...

Recommended for you

Researchers thwart cancer cells by triggering 'virus alert'

August 27, 2015

Working with human cancer cell lines and mice, researchers at the Johns Hopkins Kimmel Cancer Center and elsewhere have found a way to trigger a type of immune system "virus alert" that may one day boost cancer patients' ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.