Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative disorder. The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph) that results in the synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase (TK). The introduction of imatinib, a TK inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience a loss of response (resistance) or require treatment discontinuation because of toxicity (intolerance). In patients for whom standard-dose imatinib therapy (400 mg/day) fails, imatinib dose escalation (600-800 mg/day) is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the newer TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacologic profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historical response, adverse event tolerance level, and risk factors.
Chronic myeloid leukemia ( CML ) is a progressive and often fatal myeloproliferative disorder . The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome ( Ph ) that results in the synthesis of the BCR - ABL fusion protein , a constitutively active tyrosine kinase ( TK ) . The introduction of imatinib , a TK inhibitor ( TKI ) specific for BCR - ABL , was a major breakthrough in CML therapy . Although most patients respond to first - line imatinib therapy , some experience a loss of response ( resistance ) or require treatment discontinuation because of toxicity ( intolerance ) . In patients for whom standard - dose imatinib therapy ( 400 mg / day ) fails , imatinib dose escalation ( 600 - 800 mg / day ) is a second - line option . However , high - dose imatinib is not an appropriate approach for patients experiencing drug toxicity , and there remain questions over the durability of responses achieved with this strategy . Alternative second - line options include the newer TKIs dasatinib and nilotinib . A substantial amount of long - term data for these agents is available . Although both are potent and specific BCR - ABL TKIs , dasatinib and nilotinib exhibit unique pharmacologic profiles and response patterns relative to different patient characteristics , such as disease stage and BCR - ABL mutational status . To optimize therapeutic benefit , clinicians should select treatment based on each patient 's historical response , adverse event tolerance level , and risk factors .
What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?
What tyrosine kinase , involved in a Philadelphia- chromosome positive chronic myelogenous leukemia , is the target of Imatinib ( Gleevec ) ?
BCR-ABL
BCR-ABL