Article

The Biology of Chronic Myeloid Leukemia

Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
New England Journal of Medicine (Impact Factor: 55.87). 08/1999; 341(3):164-72. DOI: 10.1056/NEJM199907153410306
Source: PubMed

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    • "The fine regulation of ABL kinase is lost by its fusion to BCR in the context of the t(9;22). The constitutive activation of the ABL-kinase activity induces aberrant proliferation and neoplastic transformation by constitutive activation of down-stream signaling pathways such as RAS, PI3 kinase, or STATs[1,2]. Several animal models proved that BCR/ABL is responsible for the induction of the leukemic phenotype related to the t(9;22)3456. "

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    • "JID: MBS [m5G;September 21, 2015;20:38] [49]. Typically CML endures a transition from a slower chronic phase to a faster accelerated phase [48] [49]. Our model suggests that this behavior could be explained if tumor growth is first dominated by the growth rate of differentiated cells (chronic phase), and then by the growth rate of stem cells (accelerated phase). "
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    ABSTRACT: Healthy human tissue is highly regulated to maintain homeostasis. Secreted negative feedback factors that inhibit stem cell division and stem cell self-renewal play a fundamental role in establishing this control. The appearance of abnormal cancerous growth requires an escape from these regulatory mechanisms. In a previous study we found that for non-solid tumors if feedback inhibition on stem cell self-renewal is lost, but the feedback on the division rate is still intact, then the tumor dynamics are characterized by a relatively slow sub-exponential growth that we called inhibited growth. Here we characterize the cell dynamics of inhibited cancer growth by modeling feedback inhibition using Hill equations. We find asymptotic approximations for the growth rates of the stem cell and differentiated cell populations in terms of the strength of the inhibitory signal: stem cells grow as a power law t(1/k+1), and the differentiated cells grow as t(1/k), where k is the Hill coefficient in the feedback law regulating cell divisions. It follows that as the tumor grows, undifferentiated cells take up an increasingly large fraction of the population. Implications of these results for specific cancers including CML are discussed. Understanding how the regulatory mechanisms that continue to operate in cancer affect the rate of disease progression can provide important insights relevant to chronic or other slow progressing types of cancer.
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    • "The blasts in CML-BP usually have myeloid phenotype, representing 70% of the cases. Approximately 30% of cases demonstrate lymphoblastic phenotype which is predominantly B-cell lineage [3, 4]. T-lymphoblastic BP of CML is very rare and so far approximately 50 cases have been reported in the English literature [5–9]. "
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    ABSTRACT: T-lymphoblastic leukemia/lymphoma (T-ALL) presenting as blast phase of chronic myelogenous leukemia (CML-BP) is rare. In patients without history of CML, it is difficult to differentiate between CML-BP or de novo T-ALL. Here we reported 2 unusual cases of T-ALL presenting as CML-BP. Case 1 was a 24-year-old female with leukocytosis. Besides T-lymphoblasts (32%), her marrow exhibited some morphologic features of CML. Multiple remission or relapsing marrow had never demonstrated morphologic features of CML. Despite of imatinib treatment and stem cell transplant, she died 2.5 years later. Case 2, a 66-year-old male with diffuse lymphadenopathy, showed T-ALL in a lymph node and concurrent CML chronic phase (CML-CP) in his marrow. Same BCR-ABL1 fusion transcript with minor breakpoint was present in both the lymph node and marrow specimens. Although both cases did not have a history of CML, both cases represented T-lymphoblastic CML-BP with unusual features: Case 1 is unusual in that it presented as T-ALL with some CML morphologic feature but never showed CML-CP in her subsequent marrows biopsies; Case 2 is the first reported case of T-lymphoblastic CML-BP harboring BCR-ABL1 transcript with a minor breakpoint.
    Full-text · Article · Jun 2014
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