As a member of the core transcription factor family, RUNX1 plays an important role in stem cell differentiation. RUNX1 rearrangements are common in myeloid and lymphoid tumors [1]. (Blood 129(15):2070-2082, 2017). One of the most commonly detected abnormalities in acute myeloid leukemia (AML) is the translocation t(8;21)(q22;q22) (Blood Adv 4(1):229-238, 2020), resulting in a RUNX1::RUNX1T1 fusion. Occasionally, RUNX1 is translocated with other genes. This article describes an AML patient with a specific chromosomal translocation involving the RUNX1 gene and the identification of the RUNX1::WIF1 fusion. Chromosomal abnormalities were detected through karyotype analysis, break gene involved was identified via fluorescence in situ hybridization (FISH), and the novel fusion was identified through transcriptome sequencing and subsequently confirmed through reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing. A 79-year-old female patient diagnosed with AML was found to have a t(12;21)(q14;q12) translocation. FISH analysis provided evidence of RUNX1 gene rearrangement. Additionally, transcriptomic sequencing revealed a novel fusion known as RUNX1::WIF1, which consists of RUNX1 exon 2 and WIF1 exon 3. The novel fusion was further confirmed through RT-PCR and Sanger sequencing. We identified WIF1 as a novel fusion partner of RUNX1 in AML. Additionally, this is the first report of a RUNX1 fusion gene with the break point in intron 2, resulting in an out-of-frame fusion. Further research is needed to investigate the impact of this novel fusion on the establishment and progression of the disease.

目的 探讨T幼淋细胞白血病(T-cell prolymphocytic leukemia,T-PLL)小细胞变异型的临床特征.方法 对2例外周血淋巴细胞显著增高的病例,进行细胞形态学、活检病理学、骨髓免疫分型、染色体核型、荧光原位杂交(FISH)、T细胞受体(TCR)基因重排及二代基因测序(NGS)检查.结果 2例病例确诊为T-PLL,初诊时外周血和骨髓形态以成熟小淋巴细胞为主,胞体小,胞质少,胞核不规则,异型性明显,核仁不明显,符合T-PLL小细胞变异型.例1骨髓和淋巴结病理结果为CD4+CD8-T细胞淋巴瘤.2例骨髓免疫表型均为CD4+CD8-,表达泛T细胞标记CD2、CD3、CD5、CD7,且不表达CD16、CD56、CD1a、TdT、TCRγ/δ.2例TCRγ/β基因重排均为阳性.2例染色体均为正常核型,例2的FISH结果为TP53基因缺失阳性.例1的NGS结果为STAT5B、JAK3、ATM基因突变,例2的NGS结果为TP53基因突变.2例均未接受化疗,例2出院后随访1个月死亡.结论 确诊T-PLL需结合临床表现及细胞形态学、免疫分型、分子生物学、细胞遗传学等实验室检查结果综合判断,外周血细胞形态对T-PLL的诊断最为关键,免疫分型对T-PLL鉴别诊断有意义,细胞遗传学检查结果可为疾病预后判断提供依据.

目的 探讨慢性髓性白血病慢性期(Chronic myeloid leukemia-Chronic phase,CML-CP)患者治疗中酪氨酸激酶抑制荆(Tyrosine kinase inhibitors,TKI)最佳换药时机选择,为后续临床方案制定提供更多参考.方法 回顾性分析我院2015年1月至2018年12月收治的70例CML-CP患者的临床资料,均给予伊马替尼口服,分别在治疗后12周观察BCR/ABLIs和BCR/ABL拷贝数下降率,观察治疗后12个月时分子学缓解效果差异.结果 治疗12周时,BCR/ABL拷贝数下降率≥90％患者远期分子学缓解率显著高于拷贝数下降率＜90％者(P＜0.05);BCR/ABLIs≤10％者远期分子学缓解率显著高于BCR/ABLIs＞ 10％者(P＜0.05);BCR/ABLIs和BCR/ABL拷贝数下降率不同患者远期分子学缓解率比较差异有统计学意义(P＜0.05).结论 治疗早期BCR/ABLIs和BCR/ABL拷贝数下降率均可用于CML-CP患者远期分子学缓解效果预测,且两者联用可能预测价值更高;其中BCR/ABLIs＞ 10％和BCR/ABL拷贝数下降率＜90％者早期更换下一代TKI有助于改善临床预后.

Objective: To investigate the efficacy and prognosis of lung transplantation (LT) for end-stage bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The clinical data of eight cases with end-stage BOS after allo-HSCT who were treated by LT in our hospital were retrospectively analyzed. Results: Eight patients with hematological malignancy underwent allo-HSCT, and the median age was 23 (12-40) years. The donors are parents or siblings. Severe BOS occurred in 8 patients after allo-HSCT, the median age for LT was 27.5 (13-47) years. The median interval between allo-HSCT and LT was 69 (21-132) months. The median follow-up time for 8 patients after LT was 15 (6-63) months, 7 patients survived, 1 patient died of pulmonary hemorrhage 15 months after LT treatment. Of the survivors, three had BOS again, and one of them received reduplicated lung transplantation. Conclusion: LT is an effective treatment for patients with severe BOS after HSCT.

Objective:To investigate the clinical effect of second-generation tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia ( CML) . Methods:A total of 64 patients with CML treated between January 2013 and December 2016 were selected as study subjects and treated with second-generation tyrosinekinase inhibitor ( TKI) . Among them,there were 41 cases treated with Nilotinib and 23 cases with Dasatinib. In patients treated by TKI,there were 13 cases receiving first-line medication and 51 cases receiving second-line medication. All were followed up for 6 ~ 54 months,median 18 months. The overall complete hematologic remission ( CHR) rate,CCyR rate,rate of major cytogenetic response ( MCyR),MMR rate,follow-up over-all survival rate ( OS) and event free survival rate ( EFS) were observed;Meanwhile,the responses of first-line and second-line treatment and adverse drug reactions were compared. Results:At the end of follow-up,43 cases continued second-generation TKI treatment, 14 cases died, 2 cases stopped medication, 2 cases were lost to follow up and 3 cases changed the medication regimen;In terms of overall responses to treatment,the rates of CHR, MCyR, CCyR and MMR were 98. 44%, 64. 00%, 59. 37% and 43. 75% respectively; In terms of overall survival status,OS and EFS decreased with duration of the disease. The rates of CCyR,MCyR and MMR of first-line treatment were significantly higher than the second-line treatment ( P < 0.05);There were no significant differences in the incidence of adverse drug reactions between Nilotinib and Dasatinib ( P >0.05) . Conclusion:The effect of Nilotinib and Dasatinib second-generation TKI in the treatment of CML is clear. The prognosis is good and safety is better; The effect of second generation TKI first-line treatment is better than second-line treatment in treating CML.

Objective To explore decitabine combined with small dose of homoharringtonine plus cytarabine and recombinant human granulocyte colony-stimulating factor (HAG) in patients with acute myeloid leukemia to provide new ideas and new directions for clinical treatment of acute myeloid leukemia.Methods Sixty-eight patients with acute myeloid leukemia treated at Wuxi Municipal People's Hospital were selected from January 2016 to October 2016.Using a random number table,patients were randomly divided into an observation group and a control group with 34 patients in each group.The observation group was treated with decitabine combined with small dose of HAG and the control group received cytarabine plus aclamycin and granulocyte colony-stimulating factor (CAG).Treatment efficacy,and levels of CD4 +,CD8 + and CD4 +/CD8 + as well as adverse reactions were compared between the two groups.Results The overall efficacy rate was 91.2％ which was higher than 67.6％ of the control group (P ＜ 0.05).There was no significant difference in the levels of CD4 +,CD8 + and CD4 +/CD8 + between the two groups before the treatment (P ＞ 0.05).After the treatment,levels of CD4 + and CD4 +/CD8 + were significantly higher in the observation group than in the control group and CD8 + was significantly lower in the observation group than in the control group (P ＜ 0.05).Adverse reactions included gastrointestinal reactions,dysfunction of liver,respiratory infection and fever,which relieved after management of antiemesis,and liver conserving,stomach conserving therapy,albumin infusion and support treatment.There was no significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusion The capecitabine combined with low-dose HAG is effective and safe in patients with acute myeloid leukemia and is worthy of clinical promotion.

目的 探讨诱导疗法对急性髓系白血病患者临床疗效及生活质量的影响.方法 选取2012年1月至2015年12月间在无锡市人民医院进行治疗的80例急性髓系白血病患者,回顾性分析患者采用标准剂量伊达比星联合阿糖胞苷诱导治疗的不良反应、疗效及复发情况.结果 标准剂量伊达比星联合阿糖胞苷方案诱导治疗对造血系统的毒性为92.5％,对感染、脱发、胃肠道反应也有一定毒性影响.80例患者中,预后良好24例,预后中等50例,预后不良6例.预后良好患者在第1个疗程完全缓解率为54.2％,好于预后中等患者和预后不良患者,预后良好患者在各个疗程2年生存(0S)率以及2年无复发生存期(DFS)均明显高于预后中等患者.结论 伊达比星联合阿糖胞苷诱导方案治疗急性髓系白血病患者生存状况明显优于常规治疗,有利于提高患者DFS和OS率,值得推广应用.

Mammalian target of rapamycin (mTOR) as a potential drug target for treatment of acute myeloid leukemia (AML). Here, we investigated the potential anti-leukemic activity by WYE-687, a potent mTOR kinase inhibitor. We demonstrated that WYE-687 potently inhibited survival and proliferation of established (HL-60, U937, AML-193 and THP-1 lines) and human AML progenitor cells. Yet, same WYE-687 treatment was non-cytotoxic to the primary peripheral blood mononuclear leukocytes (PBMCs) isolated from healthy donors. WYE-687 induced caspase-dependent apoptotic death in above AML cells/progenitor cells. On the other hand, the pan-caspase inhibitor (Z-VAD-FMK), the caspase-3 specific inhibitor (Z-DEVD-FMK) or the caspase-9 specific inhibitor (z-LEHD-fmk) attenuated WYE-687-induced cytotoxicity. At the molecular level, WYE-687 concurrently inhibited activation of mTORC1 (p70S6K1 and S6 phosphorylations) and mTORC2 (AKT Ser-473 and FoxO1/3a phosphorylations), whiling downregulating mTORC1/2-regulated genes (Bcl-xL and hypoxia-inducible factor 1/2α) in both HL-60/U937 cells and human AML progenitor cells. In vivo, oral administration of WYE-687 potently inhibited U937 leukemic xenograft tumor growth in severe combined immunodeficient (SCID) mice, without causing significant toxicities. In summary, our results demonstrate that targeting mTORC1/2 by WYE-687 leads to potent antitumor activity in preclinical models of AML.

Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. Methods and Results: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC) to establish an in vitro iron overload model. Differentially expressed proteins initiated by the iron overload were studied by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS) analysis. We identified 93 proteins whose quantity statistically significantly changes under excess hepatocyte iron conditions. Gene Ontology (GO) analysis showed that these differentially expressed proteins in HH4 cells are involved in various biological process including endocytosis, response to wounding, di-, trivalent inorganic cation homeostasis, inflammatory response, positive regulation of cytokine production, and etc. Meanwhile, proteomics data revealed protein level of TLR2 and IL6ST significantly increased 7 times and 2.9 times, respectively, in iron overloaded HH4 cells. Our subsequent experiments detected that FAC-treated HH4 cells can activate IL6 expression through TLR2-mediated inflammatory responses via the NF-κB pathway. Conclusions: In this study, we demonstrated that iron overload induced hepatocytes triggering TLR2-mediated inflammatory response via NF-κB signaling pathway in HH4 cells.

目的 探讨白血病粒细胞缺乏期肺侵袭性真菌感染患者的病原学分布,并分析其中生化指标的改变,以期为该病的临床诊治提供依据.方法 回顾性分析2011年12月-2013年1月在医院治疗的50例白血病粒细胞缺乏期肺侵袭性真菌感染患者为真菌组,另外随机选取同时期的50例细菌感染的患者为细菌组,对真菌组进行病原学分析,并对两组患者进行生化监测,分析其在生化指标上的差异性,采用SPSS13.0软件进行统计分析.结果 白血病粒细胞缺乏期肺侵袭性真菌感染的真菌种类以白色假丝酵母菌为主,占45.1％,标本来源以痰液最常见占40.0％;检出的假丝酵母菌属除克柔假丝酵母菌外对氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑、伏立康唑等敏感率高,均＞80.0％,毛霉菌属的敏感率均为100.0％;生化指标中位值在真菌感染和细菌感染上差异明显,且两组对不同的β-D葡聚糖(1,3)和甘露聚糖的阈值也有明显的敏感性和特异性.结论 白血病粒细胞缺乏期肺侵袭性真菌感染患者的病原菌以白色假丝酵母菌为主,对氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑、伏立康唑等敏感性的真菌以毛霉菌属和光滑假丝酵母菌居多,而-β-D葡聚糖、甘露聚糖可明确真菌感染.

OBJECTIVE:JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF).METHODS:We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF.RESULTS:Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls.CONCLUSION:MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.

Bortezomib has proven to be active in patients with multiple myeloma (MM), including elderly patients. The aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with intermediate‐dose dexamethasone (Dex) and thalidomide in untreated MM patients aged ≥65 years in a Chinese single center. In this study, 18 patients were treated with bortezomib at 1.3 mg/m 2 IV on Days 1, 4, 8, and 11 and Dex at 20 mg/day IV on Days 1–4 and 8–11 simultaneously. Thalidomide at dose of 100 mg/day was given everyday. The mean number of cycles of bortezomib treatment was 2.06. Three patients (17%) achieved a complete response (CR), four (22%) a very good partial response (VGPR), and nine (50%) a PR, resulting in an overall response rate of 89%. The median time to response was 22 days (range 14–50 days). The duration of response was significantly longer in patients achieving a CR/VGPR with respect to those achieving only a PR (8.5 vs. 4.2 months, P = 0.03). Grade 3–4 toxicities occurring in patients comprised weakness, thrombocytopenia, diarrhea, infection, and neuropathy. Only one patient suffered from deep vein thrombosis. This preliminary experience in Chinese patients indicated that bortezomib‐Dex‐thalidomide is highly effective in elderly untreated patients with MM, even in patients with poor prognostic features. Am. J. Hematol. 2010. © 2010 Wiley‐Liss, Inc.

Objective To investigate the clinical efficacy of high dose dexamethasone-predominant regimens in newly diagnosed patients with multiple myeloma(MM) and renal failure(RF).Methods Medical records of 40 patients with MM and RF newly diagnosed were reviewed.Of 40 patients,22 cases(given A) were given the regimen of high dose dexamethasone and 18 cases(given B) were given additional thalidomide and/or bortezomib.Results The overall response rate(complete remission and partial remission) to chemotherapy were 50.0% and there were no significant defferences between two groups(P 0.05).The effective rate of response to the treatment was higher in the patients who achieved renal function reversal than those who did not(P 0.05).There was no significant difference in the rate of RF reversal in two groups(P 0.05).However,the median time to RF reversal was shorter in group B than that in group A (P 0.01).Logistic regression multivariate analysis showed that serum creatinine level was associated with renal function recovery.ConclusionThe addition of thalidomide and/or bortezomib to high dose dexamethasone induces a more rapid renal function reversal.Serum creatinine level is an independent factor associated with renal function recovery.

To evaluate JAK2V617F point mutation in patients with polycythemia vera (PV) and its clinical significance, the point mutation was detected by allele specific polymerase chain reaction (AS-PCR), and the clinical and laboratory features of 50 PV patients with JAK2V617F positive and negative mutations were analyzed and compared each other. The results showed that among 50 patients, 31 patients (62.0%) had JAK2V617F point mutation; 12 patients (24.0%) showed thrombosis and microvascular disturbances; 3 patients had chromosome karyotype abnormalities. As compared with negative mutation group, the age and leukocyte count in patients with JAK2V617F point mutation were older (57.5 +/- 10.0 vs 45.6 +/- 14.9, p < 0.05) and higher (16.2 +/- 6.7 vs 9.0 +/- 5.2, p < 0.05) respectively. It is concluded that the frequency of the JAK2V617F point mutation is 62.0% in PV patients, the age and leukocyte count of patients with JAK2V617F point mutation are older and higher respectively than those in negative mutation group.

Objective:To observe the efficacy and side effect of the continue low-dose Dexamethasone and thalidomide for the treatment of refractory multiple myeloma.Method:Twenty-one patients were treated with continue low-dose Dexamethasone and thalidomide.Treatment protocol was as following:Thalidomide was administered at the dose of 100mg to 200mg at bedtime and associated with dexamethasone administered orally at the dose of 1.5 mg twice a day for three months.Dexamethasone can been reduced to 1.5 mg/d after one and half months.Three months is a cycle.some patients need chemotherapy between two cycles.Result:A fall in paraprotein levels of greater than 50% was observed in six of the 21 patients and greater than 20% was observed in nine of the 21 patients.the remaining six showed disease static or progression.Treatment effective rate was 71.4%.Conclusion:We conclude that the continue low-dose Dexamethasone and thalidomide is a feasible and active regimen in the treatment of refractory multiple myeloma without intolerable side effects.

<正> 2005年3月起多个研究组报道在原发性血小板增多症(ET)等 bcr/abl 阴性慢性骨髓增殖性疾病(CMPD)中存在 JAK2基因点突变即 JAK2V617F,为该病的发病机制、诊治带来了革命性进展。由于检测方法不同,检测到 ET 中该突变发生率为23%～57%。我们收集了45例 ET 患者的外周或骨髓血 DNA,来探讨 JAK2V617F 阳性率及临床意义。

老年白血病,由于常规化疗相关的毒性和死亡率较高,因此近年来有应用阿克拉霉素、小剂量阿糖胞苷联合粒细胞集落刺激因子(G-CSF),即CAG方案治疗急性髓系白血病(AML)的报道,疗效较好,且不良反应较少.我们应用CAG方案治疗了25例老年性AML患者,也取得较好疗效.现报告如下[1].

Objective To investigate the cytogenetic features of patients with essential thrombocytemia(ET).Methods The chromosomal abnormalities of 98 newly diagnosed ET patients were studied by conventional cytogenetics(CC) and R-banding technique.SpectrumRed labeled chromosome 8 centrome specific probe and interphase fluorescence in situ hybridization(FISH) were used to detect trisomy 8 in 50 ET cases.Results CC showed 6.12%(6/98) of ET patients had chromosomal abnormalities,including 1 case with 13q-,2 with 5q-,1 with 7q-,1 with der(14)t(1;14) and 1 with Rob(13;14).FISH detected 1 case with trisomy 8 among 50 cases.Conclusion In this study,6.25% of ET patients had chromosomal abnormalities by meams of CC and no specific abnormalities were found.The frequency of trisomy 8 was low in untreated ET.

Myeloproliferative Diseases (MPD) are a spectrum of pathogenetically related disorders of varying clinical manifestations, characterized by neoplastic expansion of relatively mature granulocyte, erythroid, megakaryocyte, or monocyte and eosinocyte lineage cells. Recently a novel point mutation affecting the Janus tyrosine kinase 2 (JAK2 V617F) was identified as pathogenetically mechanisms by multiple competing groups. To investigate its prevalence and clinical significance in Chinese patients with hematological malignancies, we introduced Allele-specific PCR (AS-PCR) combined with sequence analysis to screen JAK2 V617F mutation. A total of 98 Chinese MPD patients and 120 additional hematological malignancies including AML, ALL, MDS were analyzed for the JAK2 V617F mutation. 98 MPD patients were referred for PV (n=57), ET (n=18), IMF (n=12), HES (n=2) and CML (n=9). 2 ml peripheral blood samples of MPD and 5–10 ml bone marrow samples of AML, ALL, MDS at the time of initial diagnosis were obtained with informed consent and genomic DNA was isolated presently. In addition, peripheral blood samples from 20 healthy donors were also collected as control. All samples were first screened by AS-PCR. The positive samples were subsequently confirmed by sequence analysis. The results showed that JAK2 V617F mutation was detected in 43 of 57 PV patients (75.4%), 7 of 18 ET patients (38.9%) and 5 of 12 IMF patients (41.7%). None of the AML, ALL, MDS, CML was found JAK2 V617F. There is no statistical difference of JAK2 V617F positive ratio between PV, ET and IMF. Furthermore, the mutation was not detected in the HES patient and 20 healthy controls. There is no other mutations and polymorphisms throughout exon 12 of JAK2. To our knowledge, this is the first report of JAK2 V617F mutation in a number of Chinese patients with hematological malignancies especially BCR/ABL-negative MPD. The incidence of JAK2 V617F of our study is a little lower compared with other publications especially in PV patients. The main reason may be firstly attributed to ethnic difference. In addition, with more MPD patients introduced and more sensitive methods such as ARMS-PCR or Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) applied, more JAK2 V617F mutation will be identified.