Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms

Inclusion Criteria:

• Cohort 1

• Capable and willing to provide informed consent for participation in the study.

• Diagnosis of clonal cytopenia of undetermined significance (CCUS),myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN syndrome) according to 2016 World Health Organization (WHO)classification system.

• Anemia secondary to underlying clonal cytopenia of undetermined significance (CCUS), MDS or MDS/MPN syndrome, defined as a hemoglobin <11.0 g/dL measuredwithin 30 days of study enrollment. Anemia should not be related to nutritionaldeficiency (such as iron, cobalamin, folate, or copper deficiencies),peripheral immune or non-immune hemolysis, or renal disease, in the opinion ofthe investigator.

• Age >18 years.

• Cohort 2

• Capable and willing to provide informed consent for participation in the study.

• Diagnosis of a clonal myeloid neoplasm, such as MDS, MDS/MPN syndrome,myeloproliferative neoplasm (MPN), acute myeloid leukemia (AML), clonalcytopenia of undetermined significance (CCUS), or other clonal myeloid neoplasmaccording to 2016 World Health Organization (WHO) classification system.

• A diagnosis of an otherwise unexplained Coombs-negative non-immune hemolyticanemia, according to the clinical judgement of the investigator. Some form ofobjective laboratory evidence must be present, including one or more of thefollowing: negative direct antiglobulin (Coombs) test, reduced haptoglobin,elevated indirect bilirubin, elevated lactate dehydrogenase, elevated aspartateaminotransferase, or compatible findings on peripheral blood film. Results ofall of these tests are not required to satisfy this criterion.

• Age >18 years.

Exclusion Criteria:

• Cohort 1

• Receipt of red cell transfusion within 60 days of study enrollment.

• Have a known untreated nutritional anemia or acquired disorder resulting inhemolysis, such as paroxysmal nocturnal hemoglobinuria (PNH). A knownhereditary anemia (such as thalassemia trait) is not exclusionary if thepatient's baseline hemoglobin has worsened significantly (in the opinion of theinvestigator) after development and diagnosis of MDS.

• Cohort 2

• Have a known hereditary anemic disorder, such as thalassemia, sickle celldisease, or hereditary enzyme deficiency, with the exception of hereditaryX-linked glucose-6-phosphate dehydrogenase deficiency known not to causechronic baseline hemolysis. Testing for these diagnoses is not required unlessdeemed clinically necessary.

• Have a known untreated nutritional anemia or acquired disorder resulting inhemolysis, such as paroxysmal nocturnal hemoglobinuria (PNH).