Impact of p53 in Acute Lymphoblastic Leukemia

One of the more important genes, the tp53, can be mutated in several of the malignant disorders including solid tumors as well as hematologic neoplasms.

"Our understanding for these mutations and how they affect prognosis is still somewhat limited and it's growing with time, says Dr. Moaath Mustafa Ali, a Medical Oncologist and Hematologist here at Cleveland Clinic. "Hence, observational studies become very important to understand what is the significance of these mutations on long-term survival."

In a recent episode of Cleveland Clinic’s Cancer Advances podcast, Dr. Mustafa Ali discusses the findings from a large real-world dataset about p53 and how these insights may guide future treatment strategies.

Click the podcast player above to listen to the episode now, or read on for a short edited excerpt. Check out more Cancer Advances episodes at clevelandclinic.org/podcasts/cancer-advances or wherever you get your podcasts.

Excerpt from the podcast:

Dale Shepard, MD, PhD: What did you find about the presence of the mutation in response to treatments?

Moaath Mustafa Ali, MD, MPH: In people who have a tp53 mutation, tp53 mutated acute lymphoblastic leukemia, the odds of achieving MRD, or measurable residual disease negative response, was almost 0.1 of that of people who have tp53 wild type. So that's almost like 10% of the patients will achieve an MRD negative.

So what does that translate into, that if patients have an MRD positive response and tp53 mutation and tp53 mutated ALL, that's a poor prognostic sign, and it's very rare actually to achieve MRD negativity.

Now, another thing that we found that people with tp53 mutated ALL, they have almost 60% 12-month overall survival, compared to 90% 12-month overall survival in the TP 53 wild type. So there's almost 30% difference at the 12-month mark, which is a quite big drop in survival in just one year...

The research on tp53 mutated ALL is somewhat limited..What we suggested based on our findings is that introduction of immune therapy should be considered, hopefully in clinical trials in the future in tp53 mutated ALL.