summary:

• Myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDS) typically have distinct clinical and laboratory features; however, in some patients, there is significant clinical overlap among these entities.   
• Diagnosing specific types of MDS, MPNs, and MDS/MPN overlap conditions can be challenging given overlapping clinical features and nebulous boundaries between exact diagnoses.  
• Molecular testing has particular relevance for this group of conditions as it can be helpful in the initial diagnosis as well as prognosis and treatment planning for patients who demonstrate overlap in clinical and laboratory features typically distinct for MPNs and MDS, e.g., abnormal findings on a complete blood count that include leukocytosis, anemia, and thrombocytopenia.
  • Testing may be used to both rule-out or support a diagnosis of a particular condition and should be targeted whenever clinically possible.
• Conditions with both myelodysplastic and myeloproliferative features include:
  • Atypical chronic myeloid leukemia (aCML) 
  • Chronic myelomonocytic leukemia (CMML)
  • MDS/MPN with SF3B1 and thrombocytosis (formerly Refractory Anemia with Ring Sideroblasts and Thrombocytosis (RARS-T))
  • Systemic mastocytosis (SM)

Clinical scenarios and test considerations:

The following scenarios are reasonable based on published guidelines and/or current clinical understanding:

• For patients with suspected or confirmed atypical chronic myeloid leukemia (aCML) or chronic myelomonocytic leukemia (CMML), the following genes have clinical utility:
  • ASXL1, BCR-ABL1, CALR, ETNK1, EZH2, JAK2, MPL, SETBP1, SRSF2, and TET2
    • Phenotype-specific panels (typically coded with 81450) have clinical utility and are commonly available. 
• For patients with suspected or confirmed MDS/MPN with SF3B1 and thrombocytosis, the following genes have clinical utility:
  • CALR, JAK2, MPL, SF3B1
    • Phenotype-specific panels targeted to the genes listed above have clinical utility and are commonly available. 
• For patients with suspected or confirmed systemic mastocytosis (SM), the following genes have clinical utility:
  • For diagnosis: KIT (D816V variant analysis), FIP1L1::PDGFRA fusion. (Note: KIT testing in this situation should NOT be part of an NGS panel, given low sensitivity for detection of common KIT D816V variant) 
    • The FDA-approved companion diagnostic (CDx) test for the KIT biomarker is KIT D816V Assay (ARUP Laboratories, Inc.).
  • For prognosis: TET2, CBL, JAK2, SRSF2, ASXL1, RUNX1, and RAS
    • Phenotype-specific panels (typically coded with 81450) have clinical utility and are commonly available.
• For patients with concern for recurrence (were previously in remission but have new symptoms (eg. worsening blood counts or bone marrow findings)):
  • Repeat testing via an NGS panel has clinical utility as testing may still aid in diagnosis, prognosis, and treatment decision-making of the recurrent disease.
    • While regular monitoring of blood counts and bone marrow biopsies is routine for MDS/MPN patients in remission, molecular testing is not indicated unless this routine monitoring presents a concern for relapse.
• Please note, testing should be performed on bone marrow biopsy when possible.

Medical Management:

• Are results expected to lead to a change in medical management? Yes
  • Molecular testing has demonstrated an impact to clinical care in this setting for most individuals by:
    • Guiding the selection of additional procedures (laboratory, radiology, etc.)
    • Informing prognosis
    • Directing treatment decisions
    • Informing the need for additional surveillance and/or specialty referral for management/monitoring of symptoms, e.g. ophthalmology, ENT, gastroenterology, cardiology, neurology

Related Content:

• Myelodysplastic Syndrome (MDS)
• Myeloproliferative Neoplasms (MPN)