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 PubMed
MDS AML blast percentage WHO 2022 classification
Finding Sources
Finding Sources
Searching PubMed
PTPN11 ASXL1 SF3B1 myelodysplastic syndrome prognosis
Finding Sources
Finding Sources
Reading File
Reading File
Reading File
Reading File
Reading File
Reading File
Reading File
Reading File
I now have everything needed for a comprehensive, well-sourced answer. Here it is:
Classification: MDS (with Increased Blasts) - Not AML - But with High-Risk Features
Blast Count is the Anchor
The single most important criterion distinguishing MDS from AML is the blast percentage:
| Classification | AML Blast Threshold | MDS-IB (Increased Blasts) |
|---|---|---|
| WHO 5th ed (2022) | ≥20% blasts | 5-9% (MDS-IB1) / 10-19% (MDS-IB2) |
| ICC 2022 | ≥20% blasts (OR 10-19% = "MDS-AML") | 5-9% (MDS with excess blasts) |
Your patient has ~7% blasts on aspiration. This places the case firmly in:
- WHO 5th ed: MDS with Increased Blasts 1 (MDS-IB1) - blasts 5-9%
- ICC 2022: MDS with excess blasts (5-9%) - not the MDS-AML transitional zone (which starts at 10%)
Harrison's (22nd ed, 2025) states clearly: "the WHO considers 20% blasts in the marrow as the criterion that separates AML from MDS." - Harrison's Principles of Internal Medicine 22E, p. 860
Important caveat: The aspirate was described as haemodiluted, which means the 7% blast figure may be an underestimate. The biopsy is more reliable in this context and shows "hypercellular marrow with increased blasts." If the true blast count exceeds 20% on a well-represented sample, the diagnosis would shift to AML.
Morphology Supports MDS
- Hypercellular marrow - typical in MDS (marrow is normal or hypercellular in ~80% of cases)
- Unilineage dysplasia - consistent with MDS subtypes (multilineage dysplasia would be higher risk)
- Blasts ~7% - falls in MDS-IB1 range
NGS Mutation Profile Analysis
| Gene | Frequency in MDS | Significance |
|---|---|---|
| SF3B1 | 20-25% of MDS | Splicing factor; strongly associated with MDS with ring sideroblasts (MDS-RS). Generally a favorable prognostic marker. Rarely seen in de novo AML (~10%). |
| ASXL1 | 10-15% of MDS | Chromatin modifier; truncating/frameshift mutations. Associated with adverse prognosis in MDS and AML. - Henry's Clinical Diagnosis, p. 1802 |
| PTPN11 | <1% in MDS | Rare in MDS; much more frequent in JMML (~30%). When seen in MDS/AML context, it reflects RAS pathway activation, associated with proliferative disease. - Goldman-Cecil Medicine, p. 1796 |
| IKZF1 | Uncommon in MDS | Transcription factor (Ikaros); more classically associated with B-ALL (especially Ph+ ALL) and CML blast crisis. Its presence in this myeloid context is atypical and may indicate a hybrid or high-risk molecular signature. |
Key interpretation: This mutation combination is not a "clean" MDS-RS or low-risk MDS profile. You have:
- SF3B1 (spliceosome, favourable MDS association)
- ASXL1 (chromatin modifier, poor prognosis in MDS)
- PTPN11 (RAS pathway signalling, proliferative risk, more typical of JMML or AML)
- IKZF1 (Ikaros loss; seen in transformation, CML blast crisis, aggressive disease)
The co-occurrence of ASXL1 + PTPN11 + IKZF1 in the same clone raises concern for a high-risk or evolving MDS, possibly with features of MDS/MPN overlap (CMML should be excluded - check monocyte count).
Harrison's notes: "mutations in EZH2, TP53, RUNX1, and ASXL1 correlate with poor outcome" and deep sequencing in patients whose MDS evolved to AML shows "founder clones acquiring additional mutations to become dominant clones." - Harrison's Principles of Internal Medicine 22E, p. 560
Final Diagnostic Assessment
Most likely diagnosis: MDS with Increased Blasts-1 (MDS-IB1) under WHO 5th edition
However, this is high-risk MDS with several alarming features:
- The aspirate is haemodiluted - a repeat non-diluted aspirate or a well-sampled trephine blast count is needed before finalising
- ASXL1 + PTPN11 co-mutation suggests a proliferative, high-risk molecular profile
- IKZF1 loss is unusual for typical MDS and warrants consideration of blast crisis / transformation potential
- PTPN11 mutation here should prompt monocyte count review to exclude CMML (which has its own management implications)
What would push this to AML:
- If a repeat well-sampled aspirate/biopsy shows ≥20% blasts
- If AML-defining cytogenetic abnormalities are present (e.g., t(8;21), inv(16), t(15;17)) - even at any blast percentage these are classified as AML under both WHO5 and ICC
- If t(6;9), NPM1 mutation, or biallelic CEBPA mutations are identified on expanded NGS
Recommended Next Steps
- Repeat BMA from a non-diluted site with differential blast count
- Cytogenetics/karyotype (FISH or conventional) - critical for definitive classification and IPSS-R scoring
- Monocyte count review - to rule out CMML given PTPN11 and the proliferative mutation signature
- IPSS-M score (incorporates molecular data including ASXL1) for prognosis - this will likely stratify as intermediate-high or high risk
- Haematology referral for HMA (hypomethylating agent) therapy consideration ± allo-SCT evaluation given the high-risk molecular features
Recent literature note: A 2026 comparative review (PMID: 41720165) highlights that ICC 2022 introduces an "MDS-AML" category for 10-19% blasts, which does not exist in WHO5 - if blast count edges toward 10% on repeat sampling, the ICC classification would become especially relevant for treatment decisions.
This is a shared conversation. Sign in to Orris to start your own chat.