Bone marrow biopsy (02.05.2026) : Hypercellular marrow with increased blasts and unilineage dysplasia Bone marrow aspiration (02.05.2025) : Haemodiluted marrow with presence of Atypical cells / Blasts (approx 7%) NGS : PTPN11, ASXL1, SF3B1, IKZF1 will this be MDS or AML?
Reading File
Finding Sources
Finding Sources
Searching PubMed
PTPN11 ASXL1 SF3B1 MDS AML transformation
Finding Sources
Finding Sources
Searching PubMed
myelodysplastic syndrome AML transformation blast WHO 2022 classification
Reading File
Reading File
Searching PubMed
PTPN11 mutation myeloid neoplasm prognosis AML
Reading File
Finding Sources
Finding Sources
Reading File
Searching the Web
WHO 2022 ICC MDS AML blast threshold 10% 20% IWG criteria 2023
Searching PubMed
PTPN11 SF3B1 ASXL1 IKZF1 myelodysplastic AML secondary
I now have enough information to give a thorough, well-structured answer. Let me synthesize everything.
Diagnostic Assessment: MDS vs. AML
This is a nuanced case that sits at the MDS-to-AML continuum, and the answer depends critically on the exact blast percentage in the biopsy (02.05.2026) and the classification system being applied (WHO 2022 vs. ICC 2022).
Step 1 - Reconstruct the Timeline
| Date | Finding |
|---|---|
| 02.05.2025 | BMA: Haemodiluted, atypical cells/blasts ~7% |
| 02.05.2026 | BMB: Hypercellular marrow, increased blasts, unilineage dysplasia |
The gap of exactly one year with disease progression (rising blasts, now hypercellular marrow) is significant - this is likely an evolving/progressing myeloid neoplasm.
Step 2 - Apply Blast % Thresholds (WHO 2022 and ICC 2022)
The key question is: what is the actual blast % on the 2026 biopsy?
The biopsy reports "increased blasts" but doesn't give an exact number. This matters enormously:
| Blast % (BM) | WHO 2022 Classification | ICC 2022 Classification |
|---|---|---|
| 5-9% | MDS-IB1 (MDS with increased blasts, grade 1) | MDS-IB1 |
| 10-19% | MDS-IB2 (can be treated as AML clinically) | MDS/AML (hybrid category) |
| ≥20% | AML | AML |
Key update (ICC 2022): The old MDS-EB2 category (10-19% blasts) is now replaced by MDS/AML in ICC 2022 - a hybrid category that allows patients to enter both MDS and AML clinical trials. WHO 2022 keeps these cases as MDS-IB2 but explicitly states they can be treated as AML if clinically indicated.
Step 3 - What the NGS Profile Tells You
Your mutation panel is very informative:
| Gene | Role | Clinical Significance |
|---|---|---|
| SF3B1 | RNA splicing factor | Classic MDS driver mutation - strongly associated with ring sideroblasts (MDS-RS subtype). Generally a more favorable MDS mutation. Under ICC 2022, SF3B1 mutation alone can define MDS even without morphologic dysplasia. |
| ASXL1 | Epigenetic regulator (histone deubiquitination) | High-risk MDS/AML mutation - associated with poor prognosis in MDS and secondary AML. Commonly part of the "ancestral clone" in clonal hematopoiesis. |
| PTPN11 | RAS pathway (SHP2 phosphatase) | Classically a JMML/juvenile myeloid mutation, but seen in adult MDS and AML. RAS pathway activation is an AML progression-associated mutation - it is typically a subclonal, late-event mutation acquired during transformation. Its presence is a red flag for impending or established AML evolution. |
| IKZF1 | Transcription factor (Ikaros) | Involved in lymphoid and myeloid differentiation. Mutations/deletions seen in aggressive myeloid neoplasms, associated with poor prognosis and disease progression. |
Critical observation: The combination of SF3B1 (MDS founder mutation) + ASXL1 (MDS progression) + PTPN11 (RAS pathway - AML evolution signal) + IKZF1 (aggressive biology) suggests MDS that is actively transforming toward AML. PTPN11 in particular is strongly associated with AML blast crisis in MDS patients.
Step 4 - Integrating Everything: Most Likely Diagnosis
Current working diagnosis: MDS with increased blasts (MDS-IB2) in transformation, or MDS/AML
More specifically:
- If blasts are 10-19%: MDS-IB2 (WHO 2022) or MDS/AML (ICC 2022) - treat as AML
- If blasts are ≥20%: AML with myelodysplasia-related changes (AML-MR) - the prior MDS history + unilineage dysplasia + mutation profile (ASXL1, SF3B1) all qualify this for AML-MR under both classification systems
The morphology (unilineage dysplasia only, hypercellular marrow) and the SF3B1 mutation are MDS features, but the trajectory - blast increase over 1 year, PTPN11 acquisition, IKZF1 - points strongly to active leukemic evolution.
Step 5 - What's Needed to Finalize
To give a definitive classification, you need:
- Exact blast % on the 2026 biopsy - if ≥20%, it's AML. If 10-19%, it's MDS/AML (ICC) or MDS-IB2 (WHO).
- Cytogenetics/karyotype - monosomy 5/7, del(7q), del(5q), complex karyotype all push toward AML-MR and worsen prognosis.
- Flow cytometry - immunophenotyping of the blast population to confirm myeloid lineage and exclude biphenotypic/mixed leukemia.
- Peripheral blood blast % - 1% PB blasts on two occasions qualifies for MDS-EB even without meeting BM threshold.
Bottom Line
This case is almost certainly not straightforward MDS anymore. The clinical picture is:
MDS (SF3B1/ASXL1-driven) progressing to AML, currently sitting in the MDS-IB2/MDS-AML transition zone. Treat urgently as AML with myelodysplasia-related changes (AML-MR) pending exact blast count confirmation.
The acquisition of PTPN11 (a RAS pathway mutation) is a particularly important signal - it behaves as a subclonal progression driver and is commonly acquired at the point of MDS-to-AML transformation. - Robbins & Kumar Basic Pathology, Myelodysplastic Syndromes section
Bone marrow biopsy (02.05.2026) : Hypercellular marrow with increased blasts and unilineage dysplasia Bone marrow aspiration (02.05.2026) : Haemodiluted marrow with presence of Atypical cells / Blasts (approx 7%) NGS : PTPN11, ASXL1, SF3B1, IKZF1 will this be MDS or AML?
Reading File
Finding Sources
Finding Sources
Searching the Web
WHO 2022 ICC 2022 MDS AML blast threshold MDS-IB2 MDS/AML 10-19% classification criteria
Searching PubMed
PTPN11 ASXL1 SF3B1 myelodysplastic AML progression clonal evolution
Finding Sources
Searching PubMed
PTPN11 mutation MDS AML secondary leukemia RAS pathway
Reading Web Page
MDS AML blast percentage WHO 2022 ICC 2022 classification unilineage dysplasia
You've run out of free credits. Sign up for a free account to continue using Orris.
This is a shared conversation. Sign in to Orris to start your own chat.