Category Archives: Bone Marrow

Organ Systems, Bone Marrow, WHO Classification, MDS, MDS/MPN

SB3F1 Mutation

  • SB3F1 is a RNA splicesome, mutated SB3F1 may result in an alternative function proteins instead of a loss of function mutation (Obeng, et al.)  
  • Point mutations associated with MDS are in the regions of exons 14 to 16
  • ~25% of all cases of MDS have a SB3F1 mutation
  • ~80% of MDS-RS SLD have SBF3F1 mutation
  • 30-70% of MDS-RS MLD have SB3F1 mutation
  • 20% of MDS/MPN cases have SB3F1 mutation
  • Heterozygous mutation of SB3F1 mutation is associated with disease
  • Obeng et al. demonstrated in mice that an isolated SB3F1 mutation is sufficient to cause MDS-type findings
  • The presence of a SB3F1 mutation has a positive predictive value (PPV) of finding ring sideroblasts of 97.7%.

Continue reading SB3F1 Mutation →

Organ Systems, Bone Marrow, WHO Classification, MDS/MPN, MPN

Chronic Neutrophilic Leukemia (CNL)

Diagnostic Criteria
  • Activating CSF3R mutation (usually T618I or T615A)
  • WBC ≥ 25,000 (at least 80% neutrophils + bands, <10% neutrophil precursors)
    • No dysgranulopoiesis or monocytosis (<1,000/μL)
  • Bone marrow hypercellularity
    • <5% blasts
    • Increased granulopoiesis
    • No evidence of dysgranulopoiesis
  • No molecular abnormalities or diagnostic characteristics of another MPN or MPN/MDS

If a CSF3R mutation is NOT identified, the diagnosis of CNL can still be made if other reactive causes are excluded or other evidence of clonality is identified (persistent for at least 3 months). Continue reading Chronic Neutrophilic Leukemia (CNL) →

Organ Systems, Bone Marrow, MDS

Ring Sideroblasts

General
  • Many cases of myelodysplasia (MDS-RS) and MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) are associated with SF3B1 mutations.
    • SF3B1 – splicosome gene, often comuted with JAK2 in cases of MDS/MPN-RS-T (less frequently CALR and MPL)
    • Only 5% RS is required to diagnosis MDS-RS if a SF3B1 mutation is identified.  If no mutation, then the 15% RS threshold remains.
Photomicrographs
Ringed Sideroblasts in MDS
Ringed Sideroblasts in MDS
Ringed Sideroblasts in MDS
Ringed Sideroblasts in MDS
PathMD Blog, Bone Marrow, WHO Classification

JAK2, CALR, & MPL Testing in Myeloproliferative Neoplasms (MPN)

Molecular Testing Specimen Adequacy Summary
  • JAK2, CALR, and MPL testing is often performed on peripheral blood specimens in an outpatient setting.
  • JAK2 mutations are preferably analyzed in granulocytes.
  • Peripheral blood and bone marrow specimens are equally adequate for the identification of JAK2 mutations.
  • By extrapolation, CALR and MPL testing on peripheral blood specimens should be equally adequate.

Continue reading JAK2, CALR, & MPL Testing in Myeloproliferative Neoplasms (MPN) →