HAEM5:Chronic myeloid leukaemia: Difference between revisions
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==WHO Classification of Disease== | ==WHO Classification of Disease== | ||
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Currently four FDA approved tyrosine kinase inhibitors (TKIs) - imatinib, nilotinib, dasatinib and bosutinib - are the first line of treatment for patients with newly diagnosed CML in chronic phase (CML-CP).<ref>{{Cite journal|last=Ja|first=Kennedy|last2=G|first2=Hobbs|date=2018|title=Tyrosine Kinase Inhibitors in the Treatment of Chronic-Phase CML: Strategies for Frontline Decision-making|url=https://pubmed.ncbi.nlm.nih.gov/29687320/|language=en|doi=10.1007/s11899-018-0449-7|pmc=PMC6023770|pmid=29687320}}</ref> For many years, inhibitors of the specific BCR-ABL1 tyrosine kinase are considered to be the most effective targeted therapy. A subset of CML patients can demonstrate resistance to TKI therapy through mutations in ABL1 and other mechanisms. The culprit of the resistance to TKI therapy can be attributed to so-called leukemic stem cells (LSCs), pluripotent BCR-ABL1+ progenitors that are largely quiescent.<ref>{{Cite journal|last=S|first=Tabarestani|last2=A|first2=Movafagh|date=2016|title=New Developments in Chronic Myeloid Leukemia: Implications for Therapy|url=https://pubmed.ncbi.nlm.nih.gov/27366312/|language=en|doi=10.17795/ijcp-3961|pmc=PMC4922205|pmid=27366312}}</ref> Therefore, understanding of signaling pathways related to survival of LSCs may be helpful. | Currently four FDA approved tyrosine kinase inhibitors (TKIs) - imatinib, nilotinib, dasatinib and bosutinib - are the first line of treatment for patients with newly diagnosed CML in chronic phase (CML-CP).<ref>{{Cite journal|last=Ja|first=Kennedy|last2=G|first2=Hobbs|date=2018|title=Tyrosine Kinase Inhibitors in the Treatment of Chronic-Phase CML: Strategies for Frontline Decision-making|url=https://pubmed.ncbi.nlm.nih.gov/29687320/|language=en|doi=10.1007/s11899-018-0449-7|pmc=PMC6023770|pmid=29687320}}</ref> For many years, inhibitors of the specific BCR-ABL1 tyrosine kinase are considered to be the most effective targeted therapy. A subset of CML patients can demonstrate resistance to TKI therapy through mutations in ABL1 and other mechanisms. The culprit of the resistance to TKI therapy can be attributed to so-called leukemic stem cells (LSCs), pluripotent BCR-ABL1+ progenitors that are largely quiescent.<ref>{{Cite journal|last=S|first=Tabarestani|last2=A|first2=Movafagh|date=2016|title=New Developments in Chronic Myeloid Leukemia: Implications for Therapy|url=https://pubmed.ncbi.nlm.nih.gov/27366312/|language=en|doi=10.17795/ijcp-3961|pmc=PMC4922205|pmid=27366312}}</ref> Therefore, understanding of signaling pathways related to survival of LSCs may be helpful. | ||
'''Prognosis''': Acquired resistance to imatinib therapy , mostly with mutation in BCR-ABL kinase domain, is known to be associated with poor prognosis.<ref>{{Cite journal|last=S|first=Branford|last2=Z|first2=Rudzki|last3=S|first3=Walsh|last4=I|first4=Parkinson|last5=A|first5=Grigg|last6=J|first6=Szer|last7=K|first7=Taylor|last8=R|first8=Herrmann|last9=Jf|first9=Seymour|date=2003|title=Detection of BCR-ABL Mutations in Patients With CML Treated With Imatinib Is Virtually Always Accompanied by Clinical Resistance, and Mutations in the ATP Phosphate-Binding Loop (P-loop) Are Associated With a Poor Prognosis|url=https://pubmed.ncbi.nlm.nih.gov/12623848/|language=en|pmid=12623848}}</ref> Five prognostic factors were shown to be associated with major cytogenetic response: the absence of blasts in peripheral blood, a hemoglobin level of more than 12 g per deciliter, the presence of less than 5 percent blasts in marrow, a time from diagnosis of CML to start of treatment of less than one year, and a history of cytogenetic relapse during interferon therapy.<ref>{{Cite journal|last=H|first=Kantarjian|last2=C|first2=Sawyers|last3=A|first3=Hochhaus|last4=F|first4=Guilhot|last5=C|first5=Schiffer|last6=C|first6=Gambacorti-Passerini|last7=D|first7=Niederwieser|last8=D|first8=Resta|last9=R|first9=Capdeville|date=2002|title=Hematologic and Cytogenetic Responses to Imatinib Mesylate in Chronic Myelogenous Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11870241/|language=en|pmid=11870241}}</ref> | '''Prognosis''': Acquired resistance to imatinib therapy , mostly with mutation in BCR-ABL kinase domain, is known to be associated with poor prognosis.<ref name=":1">{{Cite journal|last=S|first=Branford|last2=Z|first2=Rudzki|last3=S|first3=Walsh|last4=I|first4=Parkinson|last5=A|first5=Grigg|last6=J|first6=Szer|last7=K|first7=Taylor|last8=R|first8=Herrmann|last9=Jf|first9=Seymour|date=2003|title=Detection of BCR-ABL Mutations in Patients With CML Treated With Imatinib Is Virtually Always Accompanied by Clinical Resistance, and Mutations in the ATP Phosphate-Binding Loop (P-loop) Are Associated With a Poor Prognosis|url=https://pubmed.ncbi.nlm.nih.gov/12623848/|language=en|pmid=12623848}}</ref> Five prognostic factors were shown to be associated with major cytogenetic response: the absence of blasts in peripheral blood, a hemoglobin level of more than 12 g per deciliter, the presence of less than 5 percent blasts in marrow, a time from diagnosis of CML to start of treatment of less than one year, and a history of cytogenetic relapse during interferon therapy.<ref>{{Cite journal|last=H|first=Kantarjian|last2=C|first2=Sawyers|last3=A|first3=Hochhaus|last4=F|first4=Guilhot|last5=C|first5=Schiffer|last6=C|first6=Gambacorti-Passerini|last7=D|first7=Niederwieser|last8=D|first8=Resta|last9=R|first9=Capdeville|date=2002|title=Hematologic and Cytogenetic Responses to Imatinib Mesylate in Chronic Myelogenous Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11870241/|language=en|pmid=11870241}}</ref> | ||
'''Therapeutic implication''': Studies have shown that median survival | '''Therapeutic implication''': Studies have shown that median survival | ||