Table 3 Potential implications of... | American Society of Hematology

Table 3

Potential implications of somatic mutations of SF3B1 for molecular diagnosis and prognostication of myeloid and lymphoid neoplasms

Disorder	SF3B1 mutation
Disorder	Diagnostic significance	Prognostic relevance
MDS	The 2008 WHO diagnostic criteria for MDS¹³ are essentially based on morphology (erythroid dysplasia, ring sideroblasts, multilineage dysplasia, and excess of blasts), and include cytogenetics with respect to MDS with del(5q).	Prospective studies are required to clarify the prognostic significance of SF3B1 mutations in MDS and to resolve the current controversy on this issue.
	In perspective, searching for an SF3B1 mutation may become less expensive and more accurate than enumerating ring sideroblasts. In this context, the current RARS might become “MDS associated with SF3B1 mutation.” Combinations of SF3B1 mutation and additional mutant genes might define conditions that are associated with less favorable clinical outcome.	To date, SF3B1 appears to be the only gene for which somatic mutations are associated with a good prognosis in MDS.
MDS/MPN	The 2008 WHO diagnostic criteria for RARS-T¹³ are as follows: Refractory anemia associated with erythroid dysplasia and ringed sideroblasts 15% or greater; Fewer than 5% blasts in the BM; Platelet count 450 × 10⁹/L or greater; Presence of large atypical megakaryocytes similar to those observed in BCR/ABL1-negative MPN; and Absence of del(5q), t(3;3)(q21;q26), or inv(3)(q21q26). Future diagnostic criteria for RARS-T might include a combination of anemia and thrombocytosis as clinical parameters and a combination of SF3B1 and JAK2 or MPL mutations as molecular parameters.	Patients with RARS-T have shorter survival than those with essential thrombocythemia.⁴⁶ Analysis of SF3B1 mutation status may be useful to distinguish between the two myeloid disorders.
CLL	Unlikely to be useful for diagnosis.	SF3B1 mutations occur more commonly in advanced disease and tend to be associated with poor prognosis. Therefore, analysis of SF3B1 mutation status might be included in a targeted gene-sequencing approach to molecular prognostication of CLL. The available evidence indicates that somatic mutations of TP53, NOTCH1, and SF3B1 have independent prognostic significance.

Disorder	SF3B1 mutation
Disorder	Diagnostic significance	Prognostic relevance
MDS	The 2008 WHO diagnostic criteria for MDS¹³ are essentially based on morphology (erythroid dysplasia, ring sideroblasts, multilineage dysplasia, and excess of blasts), and include cytogenetics with respect to MDS with del(5q).	Prospective studies are required to clarify the prognostic significance of SF3B1 mutations in MDS and to resolve the current controversy on this issue.
	In perspective, searching for an SF3B1 mutation may become less expensive and more accurate than enumerating ring sideroblasts. In this context, the current RARS might become “MDS associated with SF3B1 mutation.” Combinations of SF3B1 mutation and additional mutant genes might define conditions that are associated with less favorable clinical outcome.	To date, SF3B1 appears to be the only gene for which somatic mutations are associated with a good prognosis in MDS.
MDS/MPN	The 2008 WHO diagnostic criteria for RARS-T¹³ are as follows: Refractory anemia associated with erythroid dysplasia and ringed sideroblasts 15% or greater; Fewer than 5% blasts in the BM; Platelet count 450 × 10⁹/L or greater; Presence of large atypical megakaryocytes similar to those observed in BCR/ABL1-negative MPN; and Absence of del(5q), t(3;3)(q21;q26), or inv(3)(q21q26). Future diagnostic criteria for RARS-T might include a combination of anemia and thrombocytosis as clinical parameters and a combination of SF3B1 and JAK2 or MPL mutations as molecular parameters.	Patients with RARS-T have shorter survival than those with essential thrombocythemia.⁴⁶ Analysis of SF3B1 mutation status may be useful to distinguish between the two myeloid disorders.
CLL	Unlikely to be useful for diagnosis.	SF3B1 mutations occur more commonly in advanced disease and tend to be associated with poor prognosis. Therefore, analysis of SF3B1 mutation status might be included in a targeted gene-sequencing approach to molecular prognostication of CLL. The available evidence indicates that somatic mutations of TP53, NOTCH1, and SF3B1 have independent prognostic significance.