American Society of Hematology

Case Study: Progressive Fatigue and Cytopenias in a 70-Year-Old Man

A 70-year-old man is diagnosed with leukopenia, anemia and progressive fatigue by his primary care physician and is sent for further work-up. His physical examination is unremarkable except for mild pallor of conjunctiva. His CBC is as follows:

WBC2.6 K/μL (4.0-11.0 K/μL)
Hemoglobin9.1 g/dL (13.5-17.5 g/dL)
Platelets242 K/μL (150-400 K/μL)

The bone marrow biopsy reveals a cellularity of 80 percent. Aspirate shows moderately dysplastic erythroid precursors with 19 percent ring sideroblasts. Myeloblasts are two percent.

What is the most likely mutation harbored within the patient’s bone marrow cells?

  1. FLT3
  2. SF3B1
  3. DNMT3a
  4. CTNND2

Answer

  1. SF3B1

Explanation

In 20 percent of patients with myelodysplastic syndrome (MDS) and in 65 percent of patients with MDS with ring sideroblasts, recurrent mutations of the SF3B1 gene can be found. SF3B1 encodes subunit 1 of the splicing factor 3b protein complex, a core component of the RNA splicing machinery. Patients with MDS who have this mutation have higher platelet counts, higher neutrophil counts, and most of all, longer event-free survival when compared with patients with MDS and wild-type SF3B1. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was greater than 95 percent specific for the diagnosis of secondary AML.

Case study submitted by Mark Walshauser, MD, Cancer Care Specialist of Illinois, Belleville, IL; edited by Jennifer Saultz, DO, Columbus, OH.

References

  1. Papaemmanuil E, Cazzola M, Boultwood J, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011 365:1384-1395
  2. Lindsley RC, Mar BG, Mazzola E, et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood. 2015 125:1367-1376
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