Dr. Raajit Rampal at ASH 2017 Advanced Forms of Myeloproliferative Neoplasms Are Associated with Chromosomal Abnormalities Involved in Disease Progression

Second in ASH 2017 Series

by David Wallace

Dr. Raajit Rampal is a hematology-oncology physician at Memorial Sloan Kettering Cancer Center in New York City.  In this interview we discuss “Advanced Forms of the MPNs are associated with chromosomal abnormalities involving 1q and 12q, implicating MDM2 and MDM4 in Disease Progression.”

Summary of Key Points:

  • P53 is the master regulator of the cell.  P53 becomes mutated and doesn’t function anymore in AML.
  • MDM2 and MDM4 are proteins that bind to P53 in the cell.  When they bind to P53, the cell can’t do its job.
  • Too much MDM2 or MDM4 are like having a mutation in the cell, meaning it will no longer function.
  • In certain patients who have progression of the disease, there are extra copies of chromosomes 1q and 12q and MDM2 & MDM4 which binds up the p53 causing more DNA damage.
  • Testing required – FISH analysis, looks at changes in chromosomes.
  • Mutation-Enhanced International Prognostic Scoring System (MIPSS) looks at patient factors and mutations to determine whether a patient may progress.
  • There are MDM2 inhibitors in clinical trials, drugs called Nutlins.  Activity seen in 70% of patients in PV and ET using Idasanutlin.
  • Here is the original abstract.

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