What is BCR-ABL mutation analysis?

What is BCR-ABL mutation analysis?

This test is used to determine if a mutation is present that would interfere with response to TKI therapy in Philadelphia chromosome positive (Ph+) lymphoblastic leukemia or chronic myelogenous leukemia (CML). The test detects all common mutations, including T315I.

Which is a comprehensive test for mutation analysis of resistant imatinib patients in CML?

Focus Test Summary Detects over all 90 known as well as novel mutation in the ABL kinase domain (at codon 219-506) of Ph chromosome including T3151 & P- loop mutations responsible for resistance to Imatinib.

What does p210 BCR ABL1 mean?

BCR-ABL1 fusion transcripts (p210) detected. BCR-ABL1/ABL1 quantitative ratio is provided (normalized copy number) Weakly positive. BCR-ABL1 fusion transcripts detected below the limit of quantitation.

Why is it called Philadelphia chromosome?

The abnormally shortened chromosome was discovered by both Hungerford, of the Fox Chase Cancer Center, and Nowell of the University of Pennsylvania, and was therefore named the Philadelphia Chromosome after the city in which both institutions were located.

What does dasatinib bind to?

Dasatinib functions by binding in the ATP site of the active conformation of BCR-Abl. This is unique as Abl inhibitors like Imatinib and Nilotinib bind only the inactive conformation.

What is Irma test?

This test is useful for detecting over 90 known and novel mutations in ABL kinase domain of Ph chromosome including T3151 and P-loop mutations responsible for resistance to Imatinib in CML patients.

What is the most common mutation for CML?

This study showed 43% of patients having mutations and E255V/K was the most common mutation followed by Y253H/F. The importance of presence of these mutations in CML patients on imatinib without resistance has been studied by Branford S et al.

What is the structure of a kinase domain?

Eukaryote protein kinase domains segregate into two large groups, phosphorylating either serine/threonine or tyrosine residues on target proteins. However, both groups have essentially similar three-dimensional structures comprised of two lobes with the active site located in the cleft between the small and large lobes [4,5].

How do the TYK2 pseudokinase and kinase domains interact?

The interaction between the TYK2 pseudokinase and kinase domains is predominantly mediated by the N-lobes of each domain, with the back of the pseudokinase N-lobe interacting at a near 90° angle with the underside of the kinase domain N-lobe β1–β3 sheet and the β2–β3 loop, as well as the hinge region and subsequent αD helix (Fig. 3A).

What is JAK2 pseudokinase domain?

The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol. 2011;18(9):971–976.

How do you control the activity of a kinase?

The control can be exerted by internal regions of the kinase catalytic domains, by sequences outside the catalytic domain, or by additional subunits or interacting proteins; these regions or proteins may respond to second messengers, and their expression may be controlled by the functional state of the cell.