Kaban K, Kantarjian H, Talpaz M, O'Brien S, Cortes J, Giles F J, Pierce S, Albitar M
Department of Leukemia, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Cancer. 2000 Feb 1;88(3):570-6. doi: 10.1002/(sici)1097-0142(20000201)88:3<570::aid-cncr12>3.0.co;2-i.
Chronic myelogenous leukemia (CML) represents a paradigm of the stepwise increment in disease aggressiveness, resistance to therapy, and transformation. Thrombopoietin (TPO) and its receptor, c-mpl, support the proliferation of multiple types of immature hematopoietic progenitor cells, and induce clonal growth of leukemic cells. The authors investigated whether TPO or c-mpl overexpression might correlate with progression of CML, disease aggressiveness, or response to therapy.
Expression of c-mpl and TPO was measured in bone marrow samples from 208 patients with CML by Western blot analysis and solid-phase plate radioimmunoassay (used for quantification). Samples obtained from individuals without evidence of hematologic abnormalities were used as controls.
There were no significant differences in TPO or c-mpl expression among patients in different phases of CML or between patients with Philadelphia chromosome positive and negative CML. When TPO and c-mpl levels were analyzed in relation to prognostically important host and disease characteristics in early chronic phase CML, platelet and white blood cell counts demonstrated significant differences in both TPO and c-mpl expression, but age and spleen size demonstrated significant differences in TPO expression only. Responses to interferon (INF)-alpha-based therapy and survival were not influenced by TPO or c-mpl levels.
TPO or c-mpl overexpression did not correlate with different CML phases, suggesting that they were not involved in CML progression from early to advanced phase. Neither TPO nor c-mpl overexpression was particularly evident in any risk group, suggesting lack of correlation between their expression and disease aggressiveness. This was supported by the finding of similar response to IFN-alpha-based therapy and survival regardless of the level of TPO or c-mpl expression.
慢性粒细胞白血病（CML）代表了疾病侵袭性、治疗抵抗性和转化逐步增加的范例。血小板生成素（TPO）及其受体c-mpl支持多种类型未成熟造血祖细胞的增殖，并诱导白血病细胞的克隆生长。作者研究了TPO或c-mpl的过表达是否可能与CML的进展、疾病侵袭性或治疗反应相关。
通过蛋白质免疫印迹分析和固相板放射免疫测定法（用于定量），检测了208例CML患者骨髓样本中c-mpl和TPO的表达。从无血液学异常证据的个体获得的样本用作对照。
在CML不同阶段的患者之间，或费城染色体阳性和阴性的CML患者之间，TPO或c-mpl表达无显著差异。在慢性期早期CML中，当分析TPO和c-mpl水平与具有重要预后意义的宿主和疾病特征的关系时，血小板和白细胞计数在TPO和c-mpl表达上均显示出显著差异，但年龄和脾脏大小仅在TPO表达上显示出显著差异。对基于干扰素（INF）-α的治疗的反应和生存率不受TPO或c-mpl水平的影响。
TPO或c-mpl的过表达与CML的不同阶段无关，表明它们不参与CML从早期到晚期的进展。在任何风险组中，TPO和c-mpl的过表达均不特别明显，表明它们的表达与疾病侵袭性之间缺乏相关性。无论TPO或c-mpl表达水平如何，对基于INF-α的治疗的反应和生存率相似，这一发现支持了上述结论。
