CaseVuAbstract
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal myeloid disorders that possess both dysplastic and proliferative features, but are not definitively classified as either myelodysplastic syndromes (MDS) or chronic myeloproliferative disorders (CMPD)1.
In this case study we discuss a patient with a history of MDS presenting with myeloproliferative features in the blood smear. Using only a peripheral blood sample, the findings were suggestive of MDS/MPN. Precipio’s Omnia methodology determined the patient’s mixed phenotype of disease through the application of 2 different HemeScreen® molecular panels (MPN and Cytopenia) that were necessary to properly triage the case. By doing so, they were able to identify ASXL1, SF3B1, WT1, and JAK2 V617F mutations confirming the complex diagnosis.
Case Presentation
A 75-year-old Caucasian male presented with a history of MDS, and was being treated with Vidaza. The physical examination was unremarkable; The patient had no major complaints except for fatigue. His CBC results with cell differential are presented in Table 1. The CBC showed anemia, high WBC count with abnormal differential counts.
Case Work Up &Results:
Given the complexity of the patient’s clinical presentation, the ordering physician requested that Precipio utilize the Omnia methodology.
The peripheral smear findings included an anemia without overt atypia, mild thrombocytosis with some atypical platelets, and a marked neutrophilia with left-shift, mild atypia, scattered blasts, and accompanying monocytosis. With the history of MDS, these findings were suggestive of MDS/MPN. The flow cytometry confirmed the blood smear review. To assist in correctly identifying an accurate diagnosis, additional genetic studies were performed, including FISH for BCR/ABL, JAK2 mutation analysis, as well as MDS FISH and HemeScreen Cytopenia panel. The FISH analysis was performed on uncultured peripheral blood cells and showed no evidence of an acquired clonal abnormality. For the Molecular analysis, HemeScreen MPN and Cytopenia assays were performed. The MPN panel analysis detected a point mutation in JAK2 V617F, while the Cytopenia panel detected variants ASXL1 exon 12, SF3B1 exon 16, and WT1 exon 8.
Table 1: Blood Work Up
| Test | Normal Range | Results |
|---|---|---|
| WBC (x103/μL) | 4.1 - 10.9 | 70.52 |
| RBC (x106/μL) | 4.2 - 6.3 | 2.48 |
| HGB (g/dL) | 12 - 18 | 7.54 |
| HCT | 37 - 51 | 22.5 |
| MCV (μm3) | 80 - 97 | 90.9 |
| MCH (pg) | 26 - 32 | 30.4 |
| MCHC (g/dL) | 31 - 36 | 33.5 |
| RDW% | 11.5 - 14.5 | 17.3 |
| PLT (x103/μL) | 140 - 440 | 38.1 |
| MPV ( μm3) | 7.42 - 10.77 | 9.83 |
| LYM% | 10 - 58.5 | 5.62 |
| MON% | 4.88 - 12.81 | 9.53 |
| NEU% | 40.62 - 71.65 | 82.03 |
| EOS% | 0.74 - 6.73 | 0.55 |
Clinical Implications:
The peripheral blood studies are diagnostic for myeloproliferative/myelodysplastic syndromes. The features included left-shifted neutrophilia with rare blasts, mild dysgranulopoiesis, monocytosis, anemia, borderline thrombocytosis, mutations of ASXL1, SF3B1, and JAK2 V617F, and negative FISH studies for BCR/ABL and common myeloid abnormalities. The overall features favor either the proliferative subtype of chronic myelomonocytic leukemia (CMML) or atypical chronic myeloid leukemia (aCML)2.
The preliminary presentation of this case had two possibilities to consider: either an original presentation of MDS/MPN with relatively minimal/borderline myeloproliferative features at original diagnosis, or a phenotypic transformation from MDS to an MDS/MPN, which is not an uncommon occurrence.
V617F JAK2 point mutation in myeloproliferative neoplasms (MPN) is indicated in diagnosis, classification and monitoring.
ASXL1 mutations can be seen in MDS, MPN, CMML, refractory anemia and AML. When present, the mutation is associated with poor prognosis and more aggressive disease. ASXL1 mutation often occurs in CMML (~45% of cases), and is rarely seen in PV. ASXL1 is often associated with RUNX1 cytogenetic abnormalities in both MDS and AML, as well as CEBPA in AML. Poor prognosis and aggressive disease is often paired with ASXL1 mutation.
Mutation of SF3B1 (Splicing Factor 3b Subunit 1) causes dysregulation of the maintenance of DNA. SF3B1 mutation is commonly associated with unmutated IgVH, fludarabine-resistance, and concurrent TP53 mutation. This mutation is associated with poor outcome, <10 yr survival. Studies have shown SF3B1 mutations are later events in disease progression.
Conclusions
With supporting FISH and CBC analyses, Precipio was able to confirm an aggressive mixed disease phenotype for this patient using only a peripheral blood sample, providing more comprehensive disease characterization with minimally invasive sampling.
This presentation is intended for educational purposes only and does not replace independent professional judgment. This document contains proprietary information belonging to Precipio, Inc. No use or disclosure of the information contained herein is permitted without the prior written consent of Precipio Inc.