藉由一次临床的追踪研究，科学家发现了白血病患病情恶化的分子线索，而这个发现不但有助于对这种白血病的病情发展有所了解，更有可能因此发展出治疗的新方法。
急性骨髓性白血病 (AML)是骨髓中不正常的血球细胞，不断的异常分裂所造成，目前除了以骨髓移殖的方式治疗外，临床上还可以选择用化学药物加以治疗，但统计资料显现就仅仅 20%的病人具有效果，因此深入的了解血癌细胞发病恶化的过程，一直是科学家的目标。
由德州大学安德森研究中心 Steve Kornblau医生所领导的研究团队，长期的追踪分析188 位AML 病患的临床检体，并且配合了解病患的病情发展，结果找到了3个分子标靶，参与的研究人员发现，如果病人的血癌细胞，这 3个分子都属于休眠的状态，那么确定发病后的平均存活时间，大约为 78.6周，若有 1个标的分子活化了，那平均存活时间降到57.9 周，而2 个分子同时在癌细胞里活化，那么这种病患约有42.3周的存活时间，最不幸的是血球细胞检体里 同时测到了这 3个指标分子的活动，那么病患的生命可能只剩下23.4 周。
研究人员将这一个突破性的发现 发表在最新一期血液(Blood) 期刊中并希望这样的线索，不仅仅是将来临床诊断的工具，更有机会因此而发展出新的治疗方法与治疗药物。
原始出处：
Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia
Steven M. Kornblau, Matthew Womble, Yi Hua Qiu, C. Ellen Jackson, Wenjing Chen, Marina Konopleva, Elihu H. Estey, and Michael Andreeff
Blood 2006 108: 2358-2365. Prepublished online June 8, 2006; DOI 10.1182/blood-2006-02-003475 [Abstract] [Full Text] [PDF] [Supplemental Tables]
Full Text (PDF)
Deregulation of signal transduction pathways (STPs) may promote leukemogenesis by conferring cell proliferation and survival advantages in acute myelogenous leukemia (AML). Several agents targeting STPs are under development; however, redundancy and cross-talk between STPs could activate multiple downstream effectors and this could negate the effect of single-target inhibition. The frequency of concurrent activation of multiple STPs in AML and the prognostic relevance of STP activation in AML are unknown. STP protein expression (PKC, ERK2, pERK2, AKT, and pAKT) was measured by Western blot in samples from 188 patients with newly diagnosed, untreated AML. In univariate and multivariate analysis high levels of PKC, ERK, pERK, and pAKT, but not AKT, were adverse factors for survival as was the combination variable PKC-ERK2&pERK2-pAKT. Survival progressively decreased as the number of activated pathways increased. Patients were more likely to have none or all 3 pathways activated than was predicted based on the frequency of individual pathway activation, strongly suggesting that cross-activation occurred. Simultaneous activation of multiple STPs is common in AML and has a progressively worse adverse effect on prognosis. It is thus likely that only combinations of agents that target the multiply activated STPs will be beneficial for patients with AML.
Related Article in Blood Online:
Leukemia does not live by 1 lesion alone
Judith E. Karp
Blood 2006 108: 2133-2134. [Full Text]
