Clonal hematopoiesis in IBMFS. Underlying genetic mutations lead to ineffective and stressed hematopoiesis, and ultimately HSPC attrition. Genetic variations occurred during lifetime of HSPC may confer a growth advantage if it corrected underlying genetic and/or cellular defects by somatic reversion. Alternatively, bypassing cell cycle check point by acquiring high risk genetic features, such as loss of p53, may confer a growth advantage. Clones that reverted underlying defects may have competitive advantage and higher fitness, resulting in improved counts and stable hematologic course. Whereas clones with high risk somatic alterations (eg, TP53 mutations or monosomy 7) may result in clonal expansion without functional recovery of underlying defects. These clones are more prone to acquire additional secondary mutations and/or progress to MDS/AML.