Table 3.

Frequency of ABL-kinase domain mutations by disease phase

KD MutationNo. of Mutations*No. of CP (%)No. of AP (%)*No. of BP (%)*
P-loop
    M2444733 (70)1 (2)13 (28)
    L2481310 (77)2 (15)1 (8)
    G2506331 (49)6 (10)26 (41)
    Q252143 (21)3 (21)8 (58)
    Y2536823 (34)9 (13)36 (53)
    E2556317 (27)12 (19)34 (54)
IM binding site
    D276126 (50)2 (17)4 (33)
    F31152 (40)1 (20)2 (40)
    T315569 (16)12 (23)35 (63)
    F3171510 (67)2 (13)3 (20)
Catalytic domain
    M3516233 (53)12 (19)17 (28)
    E3552213 (59)4 (18)5 (23)
    F3593521 (60)5 (14)9 (26)
Activation loop
    H3962921 (72)2 (7)6 (21)
C-terminal lobe
    S41732 (67)1 (33)0 (72)
    E45962 (33)0 (72)4 (67)
    F48680 (0)1 (13)7 (88)

Note: Adapted from Apperley (100).

Abbreviations: KD, kinase domain; CP, chronic phase; AP, accelerated phase; BP, blast phase; IM, imatinib.

  • *Number of mutations detected in a pool of patients reviewed in Apperley (100). Infrequently an individual patient harbored more than one KD mutation; any detected- mutation is included in the table.

  • Percentage of all KD mutations detected related to disease phase.

  • P-loop mutations have been inconsistently reported to be associated with a worse prognosis in comparison with other categories of mutations (55, 81, 83). Furthermore, the M244V mutation may not confer a poor outcome and has been variably included in the P-loop categories of mutations (84).