Chronic myeloid leukemia: pathophysiology, diagnostic parameters, and current treatment concepts.
Chronic myeloid leukemia (CML) is a stem cell disease characterized by excessive accumulation of clonal myeloid (precursor) cells in hematopoietic tissues. CML cells display the translocation t(9; 22) that creates the bcr/abl oncogene. The respective oncoprotein (= BCR/ABL) exhibits constitutive tyrosine kinase activity and promotes growth and survival in CML cells. Clinically, CML can be divided into three phases: the chronic phase (CP), the accelerated phase (AP), and the blast phase (BP) that resembles acute leukemia. Progression to AP and BP is associated with occurrence of additional genetic defects that cooperate with bcr/abl in leukemogenesis and lead to resistance against antileukemic drugs. The prognosis in CML is variable depending on the phase of disease, age, and response to therapy. The only curative approach available to date is stem cell transplantation. For those who cannot be transplanted, the BCR/ABL tyrosine kinase inhibitor STI571 (Glivec, Imatinib), interferon-alpha (with or without ARAC), or other cytoreductive drugs are prescribed. Currently available data show that STI571 is a superior compound compared to other drugs in producing complete cytogenetic and molecular responses. However, despite superior initial data and high expectations for an effect on survival, long term results are not available so far, and resistance against STI571 has been reported. Forthcoming strategies are therefore attempting to prevent or counteract STI571 resistance by co-administration of other antileukemic drugs. Whether these strategies will lead to curative drug therapy in CML in the future remains at present unknown.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D001856:Bone Marrow Examination; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D003937:Diagnosis, Differential; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010879:Piperazines / Q000627:therapeutic use; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D020123:Sirolimus