TY - JOUR
T1 - CML
T2 - Mechanisms of disease initiation and progression
AU - Wetzler, Meir
AU - Talpaz, Moshe
AU - Estrov, Zeev
AU - Kurzrock, Razelle
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - Chronic myelogenous leukemia (CML) is a hematological stem cell disorder characterized by excessive proliferation of the myeloid lineage. It has a progressive course typified by the transition from the chronic phase to the accelerated phase and on to blast crisis. The hallmark of CML is the translocation between chromosomes 9 and 22 that results in the chimeric BCR-ABL gene encoding p210BCR-ABL. The oncogenic potential of this protein has been validated, and it is believed that it contributes in a critical way to the initiation of CML. However, the secondary genetic forces responsible for the transition from the chronic state to the fully blastic stage are not clear. Evidence for chromosomal instability includes the clonal evolution which characterizes advanced CML. In regard to specific genetic aberrations, sporadic reports have shown alterations in H-RAS, c-MYC, retinoblastoma, and P53 genes, as well as production of p190BCR-ABL during the progression of CML. In addition, we have recently found evidence for excessive interleukin-1 β production, acting in an autocrine and/or paracrine manner, in the more advanced stages of the disease. Taken together, current data suggest that multiple molecular pathways lead to disease progression, and that distinct subsets of genetic alterations exist in blast crisis patients.
AB - Chronic myelogenous leukemia (CML) is a hematological stem cell disorder characterized by excessive proliferation of the myeloid lineage. It has a progressive course typified by the transition from the chronic phase to the accelerated phase and on to blast crisis. The hallmark of CML is the translocation between chromosomes 9 and 22 that results in the chimeric BCR-ABL gene encoding p210BCR-ABL. The oncogenic potential of this protein has been validated, and it is believed that it contributes in a critical way to the initiation of CML. However, the secondary genetic forces responsible for the transition from the chronic state to the fully blastic stage are not clear. Evidence for chromosomal instability includes the clonal evolution which characterizes advanced CML. In regard to specific genetic aberrations, sporadic reports have shown alterations in H-RAS, c-MYC, retinoblastoma, and P53 genes, as well as production of p190BCR-ABL during the progression of CML. In addition, we have recently found evidence for excessive interleukin-1 β production, acting in an autocrine and/or paracrine manner, in the more advanced stages of the disease. Taken together, current data suggest that multiple molecular pathways lead to disease progression, and that distinct subsets of genetic alterations exist in blast crisis patients.
KW - BCR-ABL
KW - Initiation
KW - Interleukin-1-beta
KW - Leukemia-myeloid-chronic
KW - Philadelphia chromosome
KW - Progression
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U2 - 10.3109/10428199309047863
DO - 10.3109/10428199309047863
M3 - Article
C2 - 8251916
AN - SCOPUS:0027181263
SN - 1042-8194
VL - 11
SP - 47
EP - 50
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - s1
ER -