Self-Renewing HSC Is the Primary Target in Pathogenesis of human CLL

饶冠华

Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic LeukemiaY. Kikushige, F. Ishikawa, T. Miyamoto, T. Shima, S. Urata, G. Yoshimoto, Y. Mori, T. Iino, T. Yamauchi, T. Eto, H. Niiro, H. Iwasaki, K. Takenaka, and K. Akashi
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Hematopoietic stem cells (HSCs) capable of self-renewal should be the main target for accumulating mutational events to develop hematological malignancies. This paper shows that HSCs also play such a role in mature lymphoid malignancies. Most human chronic lymphocytic leukemia (CLL) cases have a precursor phase, called monoclonal B lymphocytosis (MBL), that is asymptomatic monoclonal or oligoclonal proliferation of B cells. HSCs from patients with CLL but not normal HSCs developed monoclonal or oligoclonal B cells simulating MBL after xenogeneic transplantation. Acquisition of chromosomal abnormalities appeared to be secondary events to transform MBL into clinical CLL. Thus, even in CLL, accumulation of oncogenic events starts at the HSC stage. The xenograft model described in this paper might be very useful to understand the pathogenesis of human CLL., F/ P& g0 q! S1 o+ d% z2 q3 u3 p
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饶冠华

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Surprise! HSC Are Aberrant in Chronic Lymphocytic Leukemia

hughliang

类比CML和CLL，突然发现它们有很类似的地方。& l( x" U5 N+ x. h+ R. i
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LSC都可能源于HSC，其自我更新的能力源于HSC，遗传学异常赋予LSC增殖、抗凋亡优势，在CML是Ph染色体（BCR/ABL），在CLL还未知……
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, K2 e. L+ V5 s% j若CLL也如CML有疾病特征性的遗传学异常，则有可能开发类似格列卫的靶向治疗CLL的药物；但是否意味着该药物能抗增殖、诱导凋亡，却不能限制LIC自我更新的能力，即无法根治，需长期服药，犹如格列卫？5 \% T# [* }1 J  k8 H9 c
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差别呢？! y. a5 }8 C  h. s% g

& _, D" S. L6 i' a可能在于淋巴细胞的发育有赖于BCR或TCR的活化，因此抗BCR信号传递是另一个治疗思路。

hany2007

仍然只是果，而非因