Evolution of T-cell clonality in a patient with Ph-negative acute lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronic myeloid leukemia.
Evolution of T-cell clonality in a patient with Ph-negative acute lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronic myeloid leukemia.
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DOI：
10.1186/1756-8722-3-14
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发表时间：
2010-04-09
影响因子：
28.5
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang L;Zhu K;Zha X;Chen S;Yang L;Chen S;Li Y
费城染色体（pH）阴性急性白血病/脊髓降异增生综合征（MDS）在pH阳性慢性髓样白血病（CML）患者中的发展非常罕见。然而，使用CML。
为了研究一名CML患者的T细胞受体（TCR）Vα和Vβ亚家族的克隆增殖的动态变化，该患者在干扰素和伊马替尼治疗后患有pH-阴性急性淋巴细胞性白血病（全部）。
在3个时间点（诊断pH阳性慢性期（CP）CML的诊断，分别为pH-NAL的pH值和后电感化学疗法（CT）收集外周血单核细胞（PBMC）样品（pH阳性慢性期（CP）CML）。通过RT-PCR检测到TCRVα和Vβ库的CDR3大小。
5年IFN-α治疗后，CML患者在切换到伊马替尼治疗后的6个月后突然发展出pH值。在所有三个阶段都可以找到Vα/Vβ亚家族的限制性表达，而T细胞的部分亚家族则表现出克隆增殖。 -cp和pH-NENGATIC ALL。
在一名患者中检测到pH阳性CP和pH值的限制使用和克隆的亚科T细胞的限制性使用。
The development of Philadelphia chromosome (Ph) negative acute leukemia/myelodysplastic syndrome (MDS) in patients with Ph-positive chronic myeloid leukemia (CML) is very rare. The features of restrictive usage and absence of partial T cell clones have been found in patients with CML. However, the T-cell clonal evolution of Ph-negative malignancies during treatment for CML is still unknown. To investigate the dynamic change of clonal proliferation of T cell receptor (TCR) Vα and Vβ subfamilies in one CML patient who developed Ph-negative acute lymphoblastic leukemia (ALL) after interferon and imatinib therapy. The peripheral blood mononuclear cells (PBMC) samples were collected at the 3 time points (diagnosis of Ph-positive chronic phase (CP) CML, developing Ph-negative ALL and post inductive chemotherapy (CT) for Ph-negative ALL, respectively). The CDR3 size of TCR Vα and Vβ repertoire were detected by RT-PCR. The PCR products were further analyzed by genescan to identify T cell clonality. The CML patient who achieved complete cytogenetic remission (CCR) after 5 years of IFN-α therapy suddenly developed Ph-negative ALL 6 months following switch to imatinib therapy. The expression pattern and clonality of TCR Vα/Vβ T cells changed in different disease stages. The restrictive expression of Vα/Vβ subfamilies could be found in all three stages, and partial subfamily of T cells showed clonal proliferation. Additionally, there have been obvious differences in Vα/Vβ subfamily of T cells between the stages of Ph-positive CML-CP and Ph-negative ALL. The Vα10 and Vβ3 T cells evolved from oligoclonality to polyclonality, the Vβ13 T cells changed from bioclonality to polyclonality, when Ph-negative ALL developed. Restrictive usage and clonal proliferation of different Vα/Vβ subfamily T cells between the stages of Ph-positive CP and Ph-negative ALL were detected in one patient. These changes may play a role in Ph- negative leukemogenesis.