Pan Jinlan, Xue Yongquan, Qiu Huiying, Chen Suning, Zhang Jun, Wu Yafang, Shen Juan, Wang Yong
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, 188 Shizi Street, Suzhou 215006, PR China.
Cancer Genet Cytogenet. 2010 Dec;203(2):333-40. doi: 10.1016/j.cancergencyto.2010.05.009.
A pericentric inv(9)(p22q34) of the derivative chromosome 9 that resulted from a standard t(9;22)(q34;q11.2) was identified by R-banding karyotypic analysis and fluorescence in situ hybridization (FISH) assays in 4 (0.18%) of 2,200 Philadelphia chromosome (Ph)-positive leukemia patients, including 3 with chronic myeloid leukemia (CML) in chronic phase and 1 with acute myeloid leukemia (AML) in our hospital since 2004. All four patients had two malignant clones: one with only t(9;22)(q34;q11.2) and another with der(9)t(9;22)(q34;q11.2)inv(9)(p22q34) that resulted in the separation of the ABL1/BCR fusion gene. No metaphases with only inv(9)(p22q34) were seen in any of them. FISH also found a deletion of partial sequence of BCR on der(9)t(9;22)(q34;q11.2)inv(9)(p22q34) in 67.5% of bone marrow cells in the AML patient, but did not detect the deletion of the sequence of ASS/9q34 in these four patients. Reverse transcriptase-polymerase chain reaction revealed a b3a2 type of BCR/ABL1 fusion transcript in all of them, proving their disease to be Ph-positive leukemia. On reviewing the literature, only two solitary Ph-positive leukemia patients have been noticed to have the inv(9)(p22q34) anomaly. These two patients, together with our four documented patients, indicate that inv(9)(p22q34) is a novel, rare, but recurrent secondary chromosomal abnormality for Ph-positive leukemia. Despite receiving hydroxyurea therapy (n = 3 patients), combined chemotherapy (n = 2), even imatinib treatment (n = 1), three patients, including one with AML and two with CML (one of whom progressed into the lymphoblastic blast phase), died with survival times of 28 days, 13 months, and 34 months, respectively. Only one patient with CML remained alive for 5.5 months. Their negative outcome implies that inv(9)(p22q34) has an unfavorable impact on prognosis. Presently, no firm conclusions can be drawn from this study. Because the case number reported here is very small, more patients with this anomaly need to be investigated to elucidate its true prognostic significance.
自2004年以来，在我院2200例费城染色体（Ph）阳性白血病患者中，通过R带核型分析和荧光原位杂交（FISH）检测，在4例（0.18%）患者中发现了由标准t(9;22)(q34;q11.2)产生的9号衍生染色体的臂间倒位inv(9)(p22q34)，其中3例为慢性期慢性髓性白血病（CML），1例为急性髓性白血病（AML）。所有4例患者均有两个恶性克隆：一个仅携带t(9;22)(q34;q11.2)，另一个携带der(9)t(9;22)(q34;q11.2)inv(9)(p22q34)，导致ABL1/BCR融合基因分离。在这些患者中均未发现仅携带inv(9)(p22q34)的中期细胞。FISH还发现，AML患者骨髓细胞中67.5%的der(9)t(9;22)(q34;q11.2)inv(9)(p22q34)存在BCR部分序列缺失，但这4例患者均未检测到ASS/9q34序列缺失。逆转录聚合酶链反应显示，所有患者均存在b3a2型BCR/ABL1融合转录本，证实他们的疾病为Ph阳性白血病。查阅文献发现，仅注意到2例孤立的Ph阳性白血病患者存在inv(9)(p22q34)异常。这2例患者以及我们记录的4例患者表明，inv(9)(p22q34)是Ph阳性白血病一种新的、罕见但反复出现的继发性染色体异常。尽管接受了羟基脲治疗（3例患者）、联合化疗（2例），甚至伊马替尼治疗（1例），但包括1例AML和2例CML（其中1例进展为淋巴细胞母细胞急变期）在内的3例患者分别在28天、13个月和34个月死亡。仅1例CML患者存活了5.5个月。他们的不良结局表明inv(9)(p22q34)对预后有不利影响。目前，本研究无法得出确凿结论。由于此处报告的病例数非常少，需要对更多有这种异常的患者进行研究，以阐明其真正的预后意义。
