Biomarkers — the key to progression
Foundation launches researcher/patient project to unmask MPNs
Questions: Will your essential thrombocythemia or polycythemia vera progress to myelofibrosis? Is your myelofibrosis tilting toward acute myeloid leukemia?… When is a stem cell transplant needed?…Which clinical trial makes the most sense? Do your meds work?
The answers to all those questions depend on precise knowledge of biomarkers. Those molecular signposts signal the onset or progression of disease as well as our resp0nse to treatment.
Not only do we not yet have a road map of all biomarkers driving our MPN do we not currently know the impact of more than a handful. Without these signs we are in the dark.
That’s all about to change. . .
The MPN Research Foundation is getting ready to announce its revolutionary, strategic commitment to get at the molecular root of myeloproliferative neoplasm pathology. The Progression Marker Project is a budding alliance of participating MPN research centers committed to uncover the key molecular biomarkers driving progression of MPNs from chronic ET and PV to myelofibrosis.
Conceived in concert with leading researchers — including MD Anderson’s Dr. Srdan Verstovsek, anticipated Principal Investigator — the PMP will be a long-term funded international joint effort pooling tissue data from MPN patients along the complete MPN pathway. “Our project,” says Verstovsek,” will focus on fibrotic transformation which has been neglected so far in academic circles, unlike leukemic transformation.”
And while institutions and drug companies may be contributing to the effort, patients and caregivers now have a vehicle to collectively bankroll a substantial part of the work through the newly announced Harvey Gould Fund.
JAK2 V617F mutation is the biomarker most all MPN patients and caregivers know. Currently, it is the most significant biomarker in myeloproliferative neoplasms. CALR, occurring in about half of ET and MF patients with normal JAK2, is second. While the JAK2 biomarker has driven much drug research — and over a billion dollars in prescription revenues — it is clearly only a minor part of the MPN genesis and progression story. Jakafi has produced short-term benefit for many MPN patients but it does not stop the progression of disease. Nor is the JAK2 mutation definitive for diagnosis. (We can have an MPN without it and not have an MPN with it.) We need a much fuller picture of associated biomarkers and the responses of each to provided treatment to start unraveling the mystery of MPNs.
To get that information we need patient participation, says Verstovsek, “and standardized treatment of MPN tissue samples, monitoring of responses to treatment over time by diverse patient populations, deep sequencing of targeted genes, shared tissue samples — and results — across research institutions. ” That is the promise of the MPNRF Progression Marker Project.
“In the absence of such molecular biomarkers,” according to the International Working Group for MPN Research and Treatment, “efficacy results may be misleading…. Molecular biomarkers would allow stratification of patients for molecular risk or molecular pathogenesis.”
Today, signs of MPN progression – the indicators that dictate treatment options – are fairly crude and imprecise. Prognostic scales are based on blood values, patient age, clinical presentation and a few mutations that, while likely accelerating disease, surely do not cause it.
Now, instead of supporting another lookalike JAK inhibitor or some experimental drug, we can invest our money and energy directly into precision medicine laser focused on MPNs. We can help find the source of the genetic mayhem that turns our blood into a rampaging out of control enemy. And start building a map of the signs and signals that tell us precisely when our MPN is on the move…and how fast and far it’s headed…and how effective specific meds are in defined molecular environment.
Here’s how it would work
Preliminary Foundation plans call for an initial launch with three sites: Northwestern, Memorial Sloan-Kettering and MD Anderson, adding sites over time. Each lab would follow a common protocol which would include enrolling patients and ensuring consistent collection, protection and transfer of data. The clinical data and results from sequencing would be combined, and this dataset then made available to MPN researchers.
We can join in this crusade by investing in the Harvey Gould Fund, a war chest launched by the Gould family, exclusively devoted to the MPN Research Foundation’s massive effort to map biomarkers, the engine of MPN progression. All net proceeds invested in the Harvey Gould Fund will be restricted to biomarker research managed by the Foundation. You can make your donation right here.
Harvey Gould, an MPN patient, a San Franciso based attorney and much beloved MPNforum columnist and editor was an integral part of the very first MPNforum generation.
His monthly column, The Long and Winding Road, was a gentle, often humorous commentary on MPNs, his wife, Karen, his love of family, horses and Ireland. But mostly, through encouraging words and his personal example, he was a staunch supporter of MPN patients.
It was on his account that his daughter Ashley initiated the 23andMe MPN program that enrolled 1000 patients for free DNA studies building the likely largest anonymized database of MPN patients’ DNA, available to researchers. (Dr. Jason Gotlib’s recent findings on the origins of MPNs is owed to Harvey Gould’s efforts in building this initiative.)
Harvey participated in the Gotlib-led Stanford CYT-387 clinical trial from which he was removed when his MF progressed to acute myeloid leukemia. He succumbed after his AML grew out of control despite a belated attempt at stem cell transplant.
Had he and his physicians known the status of his progression biomarkers it’s possible he would not have wasted so much precious time in clinical trial but started his stem cell transplant with much more favorable odds in his favor. With Harvey’s strong presence in our community and the efforts of his family and the MPN Research Foundation, future generations may well step out of the darkness of MPN progression and receive timely, precise treatment. You can help by donating here.
(On September 13 we observed the third anniversary of the passing of Harvey Lawrence Gould.)