Figure 2.

SF3B1-K700E mutation occurs in CLL2 HSC+MPP fraction, whereas SF3B1-I704F mutation is only detected further down in the hematopoietic differentiation pathway. (a) Detection of SF3B1-K700E in CLL2 HSC+MPP fraction. Although SF3B1-I704F was present in mature CLL2 B cells, deep sequencing analysis did not detect this mutation in the HSC+MPP population of CLL2, or in the control undiluted and 1:10³ diluted mature CLL4 B-cells (VAF <0.01%). However, SF3B1-K700E was identified in both CLL2 HSC+MPP and in the companion mature B cells (VAF >0.15%), as well as in undiluted and 1:10³ diluted mature CLL4 B-cells at expected VAFs. (b) Graphical representation for the pattern of SF3B1 mutations identified in CLL2 by targeted sequencing at >630 000 depth. SF3B1-I704F was identified with a VAF of 47% by WES in the leukemic clone but was not found in the HSC+MPP fraction (VAF <0.01%). SF3B1-K700E mutation was present in the HSC +MPP fraction (VAF >0.15%), and the same abundance was maintained in the mature CLL B-cell clone (VAF >0.15%).