Fig. 3.1 Formation of BCR-AB fusion gene by reciprocal chromosomal translocation t(9;22) and their breakpoints There are several functional domains in BCR-ABL, through which it interacts with downstream signaling molecules…
Fig. 9.1 Overall cytogenetic and molecular response rates of chronic phase CML to ponatinib within the PACE trial [14]. MCyR states for major cytogenetic response, CCyR for complete cytogenetic response,…
Disease phase ELN (2006) WHO (2008) ELN (2013) Accelerated phase Blast cells in blood or bone marrow 15–29 %, or blasts + promyelocyte in blood or marrow >30 %, with blasts <30 % Blast cells…
Fig. 12.1 Rates of treatment-free remission in the (a) STIM and (b) TWISTER clinical trials. Kaplan-Meier estimates of the proportion of patients free of molecular recurrence after imatinib withdrawal. The…
Mechanism of resistance Treatment strategies BCR-ABL1-dependent ABL1-kinase domain mutationsa Second-generation TKIs Ponatinib [77, 78] or allosteric inhibitors BCR–ABL1 amplification BCR-ABL1-independent (intrinsic) Activation of downstream signalling JAK-STAT pathway PI3K/AKT/mTOR pathway JAK2…
Imatinib Nilotinib Dasatinib Bosutinib Ponatinib First line, approved dose 400 mg OD 300 mg BID 100 mg OD NA NA Second line, approved dose 300–400 mg BID 400 mg BID 70 mg BID or 140 mg…
Time First line Second line Optimal response Failure Optimal response Failure Baseline 3 months BCR-ABLIS ≤10 % No CHR BCR-ABLIS ≤10 % No CHR or Ph+ >95 % or mutations Ph+ ≤35 % Ph+ >95 %…
Method Target Sensitivity Advantages Disadvantages Metaphase t(9;22) 1–5 % The gold standard and detection of other chromosomal changes Needs dividing cells, so generally only successful form of bone marrow sample Chromosome…
Fig. 2.1 CML stem cell maintenance. CML stem cells self-renew as HSCs do when BCR–ABL kinase activity is inhibited by tyrosine kinase inhibitors (TKIs). Therefore, survival of CML stem cells…
Reference N Response C0 (ng/mL) P value N ≤1000 N >1000 Marin et al. [10] 84 CMR 43 23.3 % 41 44.4 % 0.14 MMR 60.1 % 83.2 % 0.02 Takahashi et al. [41]…
