Clinical Case Discussion Forum

To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML cases here. Physicians submit a brief history of the patient and the case for discussion using this forum.

Molecular Monitoring

Topic Molecular Monitoring was created by Dr Udani Sajitha Kothalawala
Dr Udani Sajitha Kothalawala Sri Lanka 06:08 11 August 2025

Hello, Recently we have come across a patient with both p210 and p190 transcripts at diagnosis. What is your experience with a case like this and its molecular monitoring and management considerations? Awaiting your reply. Best regards - Udani (Registrar in Haematology, Sri Lanka)

Reply by Professor Jerry Radich on topic Molecular Monitoring
Professor Jerry Radich USA 06:25 11 August 2025

What are the levels of each transcript type? It is often common for cases of p210 disease to have very low levels of the p190 transcript at diagnosis, and this is believed to be a splicing event with no impact on prognosis.

Reply by Professor Gianantonio Rosti on topic Molecular Monitoring
Professor Gianantonio Rosti Italy 06:24 12 August 2025

"Both p210 and p190" in which %? Generally, p210 is predominant (1-2% of all CP patients may exhibit this association). However, there are data supporting a worse prognosis for patients bearing the association. Generally, those who progress do so in the early days.

I understand you do qualitative RT QPCR at diagnosis due to financial pressures of many patients, but it’s important to follow-up with quantitative monitoring of the highest burden. It is important to know at diagnosis if p190 is a small fraction or the highest burden. Generally, it is a small fraction and disappears rapidly. If prevalent, this notion has relevant prognostic features with p190 bearing a worse prognostic meaning vs p210.

To be practical, in terms of management, there is no strong data in favour of second gen TKIs vs imatinib. Monitoring is as per p210 only patient.

Reply by Professor Giuseppe Saglio on topic Molecular Monitoring
Professor Giuseppe Saglio Italy 06:26 13 August 2025

The P190 transcripts derive from alternative splicing and therefore you must follow the predominant e13 or e14 BCR/ABL type of transcript.

Reply by Dr Delphine Rea on topic Molecular Monitoring
Dr Delphine Rea France 06:27 19 August 2025

Usually e19a2 constitute a minority and most CML MRD is made of Major transcripts.
Monitoring should thus be done using major transcript tools.

Reply by Dr Jeff Lipton on topic Molecular Monitoring
Dr Jeff Lipton Canada 06:27 20 August 2025

I agree with Delphine and I think it is important to put this into perspective. A large part if not majority of the world does not have access to accurate and timely pcr monitoring. Those of us with a lot of resources at our fingertips often forget this. Monitor what can be done readily and that should support the patients. Perhaps in the future, all of us will have access to all drugs and all technology.

Reply by Professor Akhil Ranjan Biswas on topic Molecular Monitoring
Professor Akhil Ranjan Biswas Bangladesh 06:28 20 August 2025

Given expression of two BCR-ABL1 transcript, I would prefer to monitor by P210 if monitoring facility for both transcript is not available, as P210 is likely to by the transcript of primary clone. However, considering that p190 is coming from a subclone, I would prefer to do hematological monitoring by CBC more frequently, may be monthly to detect any probable hematological relapse from that subclone.

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