Pre­dict­ing risk of ag­gres­sive form of leukemia

Ge­netic screen­ing tool can help an­swer where, when and how the dis­ease be­gins, say re­searchers

The Recorder & Times (Brockville) - - ENTERTAINMENT - SH­ERYL UBELACKER

TORONTO — Symp­toms of acute myeloid leukemia tend to arise quite sud­denly, but sci­en­tists have dis­cov­ered signs of this ag­gres­sive, deadly form of blood cancer can be present many years ear­lier — pro­vid­ing hope for a treat­ment that could stop the dis­ease from ever oc­cur­ring.

A team of Cana­dian and in­ter­na­tional re­searchers has dis­cov­ered a way of pre­dict­ing if healthy in­di­vid­u­als risk de­vel­op­ing acute myeloid leukemia, or AML, up to a decade be­fore its on­set.

The find­ings, pub­lished ear­lier this week in the jour­nal Nature, an­swer the ques­tion of where, when and how the dis­ease be­gins, said John Dick, a se­nior sci­en­tist at Princess Mar­garet Cancer Cen­tre in Toronto and a co-prin­ci­pal au­thor of the study.

“We have been able to iden­tify peo­ple in the gen­eral pop­u­la­tion who have traces of mutations in their blood that rep­re­sent the first steps in how nor­mal blood cells be­gin on a path­way of be­com­ing in­creas­ingly ab­nor­mal and puts them at risk of pro­gress­ing to AML,” said Dick.

AML, the most com­mon type of leukemia in adults, be­gins in stem cells within the bone mar­row that have picked up a ge­netic mu­ta­tion. It causes them to pro­duce im­ma­ture white blood cells called myeloblasts. Over time, these dys­func­tional cells take over and crowd out healthy cells, re­sult­ing in leukemia.

Symp­toms in­clude fever, bone pain, fa­tigue, short­ness of breath, fre­quent in­fec­tions, bruis­ing and un­usual bleed­ing, such as re­cur­ring nose­bleeds and bleed­ing from the gums.

More than 1,300 Cana­di­ans de­velop AML each year, ac­cord­ing to 2013 es­ti­mates from the Cana­dian Cancer So­ci­ety. Al­most 1,050 died of the dis­ease that same year.

Men are more likely than women to de­velop this kind of leukemia. Risk in­creases with age, with the blood cancer oc­cur­ring most com­monly in adults age 65 and older.

“AML is a dev­as­tat­ing dis­ease di­ag­nosed too late, with a 90 per cent mor­tal­ity rate af­ter the age of 65,” said co-au­thor Sagi Abel­son, a post-doc­toral fel­low in Dick’s lab.

The cur­rent study builds on Dick’s 2014 dis­cov­ery that a preleukemic stem cell could be found lurk­ing among all the leukemia cells present in a blood sam­ple taken when a per­son is first di­ag­nosed with AML. The pre-leukemic stem cell still func­tions nor­mally but has taken the first step in gen­er­at­ing cells that be­came in­creas­ingly ab­nor­mal.

“So what we had done was we had cap­tured pre-leukemia, we had cap­tured the idea that there is a stem cell that has picked up a mu­ta­tion and it can sit there pre­sum­ably for some pe­riod of time and start to take over the blood be­fore you ac­tu­ally get leukemia,” Dick said.

“It pre­dicted that if we sam­pled the gen­eral pop­u­la­tion, we might be able to find in­di­vid­u­als who are at risk for de­vel­op­ing leukemia long be­fore they ac­tu­ally have leukemia.”

To con­duct the study, the sci­en­tists turned to a Euro­pean re­search pro­ject that had en­rolled 550,000 peo­ple and fol­lowed them for about 20 years, look­ing for health and lifestyle fac­tors that might be associated with the devel­op­ment of different types of cancer.

They found the blood sys­tem had be­gun pick­ing up mutations years be­fore a di­ag­no­sis of leukemia, a find­ing that en­abled the team to pre­dict with “very high ac­cu­racy” who had been at risk of de­vel­op­ing the dis­ease.

“What the data show is the dis­ease has had a long evo­lu­tion and our nor­mal stem cells are the reser­voir in which this evo­lu­tion hap­pens,” said Dick. “This is giv­ing us huge in­sight into the mech­a­nism of how leukemia de­vel­ops from within a nor­mal stem cell and the path­way that it takes.”

UniVeR­siTy heaLTh neTWoRK Via The cana­dian PRess

John Dick, se­nior sci­en­tist at Princess Mar­garet Cancer Cen­tre.

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