骨髓MR功能成像监测高风险表型AML小鼠化疗有效性的研究

Chromosome aberration is an independent chemotherapeutic and prognostic factor to acute myeloid leukemia. However, the clinical outcome of normal kayotype AML patients with different cytogenetic subset has varied among pre-studies. Now the micro-environment change of bone marrow with high-risk cytogenetic subset in different stages (newly diagnosed, complete remission(CR), and overall survival(OS)) are not well characterized and the relapse risk are not well prognosticated..The study aim to detect the micro-structure character of bone marrow by MR spectrum and MR perfusion technique in high-risk prognostic category AML mice with c-Kit(+) cytogenetic subset. To evaluate the fat cell and AML blast cells character through detecting the ratio of unsaturable and saturable fatty acid and the microvessel density in AML mice bone marrow with different SHP-1/c-Kit expression. .The study try to explore the AML marrow change mechanism on angiogenesis, myelomonocytic cell accumulation, the amount of fat cells and AML blast cells through analyzing the pathology mechanism of MR intensity character with the marrow structure change. We hope to provide another effective method to monitor the therapy effect in AML patient with high-risk gene phenotype.

染色体核型被作为急性髓系白血病（AML）的独立预后因素，但正常核型、不同基因表型AML化疗预后异质性较大，目前存在的问题是高风险表型AML患者化疗缓解、复发预后判断缺乏十分有效的方法。本研究拟采用无创的MR波谱成像和MR灌注成像检测SHP-1/c-Kit不同表型 (AML)小鼠骨髓微结构特征，通过饱和/不饱和脂肪酸比例变化监测以及骨髓微血管密度变化及灌注状态监测，进行不同SHP-1/c-kit表型AML小鼠骨髓脂肪细胞、白血病细胞分布特征研究。力图通过MR信号强度改变的病理基础研究阐明不同SHP-1/c-Kit表型AML在治疗不同时期骨髓血管生成、粒单核细胞增殖的发生机制，以期能够无创监测、判定AML骨髓浸润的类型、程度以及化疗疗效，为今后高风险基因表型AML患者进行选择性治疗和疗效监测提供思路 。

不同基因表型AML骨髓浸润、化疗预后异质性比较大，但目前高风险表型AML患者骨髓浸润程度、治疗后缓解、复发的预后判断缺乏十分有效的方法。本研究通过流式细胞仪检测AML-M4型小鼠c-Kit/Mac3表型，通过外周血涂片、骨髓切片判定不同程度骨髓浸润状态下骨髓内白血病细胞分布、骨小梁基质变化特征，通过microCT半定量测量椎体骨矿含量、并与MR波谱测定脂肪峰值变化进行相关性研究；通过骨髓微血管密度变化与MR灌注曲线相关性研究，发现不同c-Kit/Mac3表型AML在不同时期骨髓血管生成、粒单核细胞增殖情况不同；骨髓浸润程度增加，骨小梁体积减少、骨矿含量减低、骨髓脂肪含量减低、血微循环灌注状态增加。本研究提示MR波谱、灌注成像可以判定AML骨髓浸润的类型、程度，为今后高风险基因表型AML患者进行选择性治疗和疗效监测提供思路。