Ultra Assesses Deep Molecular Response in Chronic Myeloid Leukemia Patients on Treatment with Tyrosine Kinase Inhibitors
The very high (arguably, complete) association of the BCR-ABL
fusion with this disease led to early efforts at standardizing a molecular method of MRD quantification.
Iclusig targets not only native BCR-ABL
but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.
MR4 is achieved with a BCR-ABL
expression of <0.
Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL
transcripts and kinase domain mutations and for expressing results.
At 3 months, 84% of evaluable patients receiving dasatinib achieved ≤ 10% BCR-ABL
levels vs 64% of imatinib treated patients (p=0.
This t(9;22) translocation results in the formation of the BCR-ABL
fusion gene, which codes for a novel protein tyrosine kinase (TK) that is constitutively activated and therefore leads to increased proliferation of myeloid cells, decreased apoptosis and adhesion, and genetic instability of the leukaemic cells.
The team tested whether Stat3 and Stat5, acting downstream of Bcr-Abl
are critical for leukemia maintenance andAaif they could be a alternative target for treatment.
The team, led by Dr Veronika Sexl from the University of Vienna, conducted their research on acute lymphoid leukaemia (ALL) and chronic myelogenous leukaemia (CML), which can both be caused by fusion protein, Bcr-Abl
, created through the joining of two or more genes originally coded for separate proteins.
Imatinib mesylate, an inhibitor of Bcr-Abl
tyrosine kinases, has revolutionized the treatment of chronic myelogenous leukemia (CML), showing marked improvements in survival in all three phases of the disease: chronic, accelerated, and blast crisis (see Figure 1).
MK-0457 (also known as VX-680) is an investigational small molecule inhibitor of Aurora, FLT-3, JAK-2 and BCR-ABL
, this abnormal protein causes the leukemia by disconnecting the brakes on cells' replication machinery.