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Abdul Mannan: The Hardest Conversations in Myelofibrosis

Abdul Mannan/LinkedIn

May 18, 2026, 16:01

Abdul Mannan: The Hardest Conversations in Myelofibrosis

Abdul Mannan, Consultant Haematologist at Betsi Cadwaladr University Health Board, shared a post on LinkedIn:

”Myelofibrosis is the hardest MPN to face.

For patients and for us.

Bone marrow replaced by scar tissue.

Spleen the size of a football. Fatigue that doesn’t lift.

And a prognosis that forces you into some of the most difficult conversations in haematology.

So when we risk-stratify, we have to get it right.

Here’s the simplest way to remember the molecular picture:

CALR type 1 equal the one favourable signal in a tough disease. Better survival. The kindest mutation MF offers.
ASXL1, SRSF2, EZH2, IDH1/2 equal high-risk mutations that drive faster progression and worse outcomes.
U2AF1 Q157 equal now formally recognised as adverse in MIPSS70 plus v2.0 and GIPSS. A newer addition to an already difficult list.
Getting this molecular profile right decides who needs transplant, and when.

MIPSS70 plus v2.0 (Guglielmelli et al., Journal of Clinical Oncology, 2018) and GIPSS (Passamonti et al., Leukemia, 2017) both integrate these mutations into risk scoring. These aren’t just academic exercises. They shape real decisions for real patients.

Memory line for trainees: CALR type 1 is kind. The rest are not.

In a disease this serious, clarity in risk assessment is the least we can offer our patients.

What’s the toughest MF conversation you’ve had with a patient recently?”

Abdul Mannan: The Hardest Conversations in Myelofibrosis