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Acute basophilic leukemia (ABL) arising from chronic myeloid leukemia (CML) with abundant mast cells (MCs), coexisting with a complex karyotype is rare. Here, we report an 81-year-old man admitted to our hospital with a history of ABL. He was diagnosed with CML in the chronic phase in January 2018, and Imatinib was used at a daily dose of 400mg. Then, transformation to ABL with abundant MCs in the bone marrow and complex karyotypes including 48,XY, trisomy 8 (+8), isochromosome 17(q10) [i(17)(q10)], and derivative chromosome 22 t(9;22) [der(22)t(9;22)] were discovered simultaneously in January 2022. In conclusion, the increased number of MCs in our case is a reminder that they might play an important role in the prognosis of CML and trigger the development of complex karyotypes. Moreover, this is the first case report of ABL arising from CML with abundant MCs, coexisting with 48,XY, +8, i(17)(q10), and der(22)t(9;22), during Imatinib treatment. Further studies are needed to better characterize this rare condition.

BACKGROUND: Adult acute myeloid leukaemia (AML) patients with complex karyotype (CK) generally have unfavourable outcomes. CK commonly co-exists with characteristic chromosomal and genetic abnormalities such as monosomal karyotype (MK), -17 or 17p- [abn(17p)] and TP53 mutations. Their individual prognostic significance needs to be clarified.
METHODS: Seventy-three adult CK-AML patients and eleven adult non-CK-AML patients with TP53 mutations (non-CK/TP53mu ) who were diagnosed and received therapy at our institute were enrolled. One hundred and fifty-seven AML cases retrieved from the cancer genome atlas (TCGA) for validation.
RESULTS: Among CK-AML patients, those with TP53 mutations (CK/TP53mu ) had significantly lower rates of 1-course induction complete remission (CR), 2-year relapse-free survival (RFS) and 2-year overall survival (OS) than those without TP53 mutations (CK/TP53wt ); whereas, abn(17p) did not have the above impacts; MK was significantly associated with a lower 2-year OS rate but was not related to the rates of CR and RFS. Multivariate analysis showed that it were TP53 mutations and treating with chemotherapy alone but not MK and abn(17p) that independently predicted the adverse prognosis for RFS and OS in CK-AML. Furthermore, non-CK/TP53mu patients showed similar rates of CR, RFS and OS to CK/TP53mu patients. Validation using the TCGA cohort showed that CK/TP53mu patients had a significantly lower 2-year OS rate than CK/TP53wt patients, whereas abn(17p) and MK did not impact OS; the 2-year OS rate of patients with CK/TP53wt was similar to that of patients with intermediate-risk cytogenetics.
CONCLUSIONS: Adult CK-AML patients have varied risks and TP53 mutations seem to be an independent adverse prognostic factor.

UNASSIGNED: A translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 which is a rare cytogenetic abnormality in CLL patients, has a more aggressive clinical course with a shorter time to first treatment (TTT) and worse overall survival (OS). To date, there is no literature reporting the identification of the t(14;19) in Chinese CLL patients and the reviewing the characteristic of all patients with this abnormality reported previously in the literature.
UNASSIGNED: We first demonstrate three cases of t(14;19) translocation among the 200 CLL patients from 2017 to 2019 in our hospital. We investigated several aspects such as clinicopathologic features, cytogenetic analysis, IGHV mutations, next-generation sequencing technology (NGS), and histopathological characteristics in order to clearly define the features of this entity in Chinese patients and compare them with patients reported previously in western countries.
UNASSIGNED: The clinical and pathological features of our three cases resemble those of earlier reports. All patients had atypical morphologic features and atypical immunophenotypes with low CLL scores detected by flow cytometry. All cases were unmutated in the IGHV mutations. Two cases showed complex karyotype and one case demonstrate missense mutations of TP53 and FBXW7.
UNASSIGNED: In conclusion, this is the first report on IGH/BCL3-positive B-CLLs in Chinese people, which provided a comprehensive analysis of clinical and pathological characteristics. In addition to some similar clinical and laboratory features reported in the previous literature, we first found that CLL with t(14;19) has a higher possibility of being accompanied with high complex karyotype (high-CK), which is now regarded as a novel negative prognostic marker. Early identification of this abnormality in CLL patients is so important that patients can benefit from the more aggressive treatments at the onset of the disease.

Chromosomal aberrations play an important role in the incidence of myelodysplastic syndromes (MDS) and development to acute myeloid leukemia (AML). We report a case of a 62-year-old male patient diagnosed with MDS with excess blasts. The karyotype was 45, XY,+1,+1,-7,-10,-22,t(1;14) (q21;q32),t(1;17)(q21;p13),t(1;19)(q21;p13). The patient and his family refused treatment for financial reasons. After 2 months, the patient\'s MDS transformed into acute myeloid monocytic leukemia (AML-M5). This case of MDS with poor prognosis shows that patients with chromosomal numerical abnormality and balanced translocations should be treated early to prevent transition to AML. Further study of this case will reveal the molecular mechanism of MDS-to-AML transformation and identify new leukemic fusion genes.

OBJECTIVE: Diffuse Large B-Cell Lymphoma (DLBCL), NOS, constitutes 25-35% of adult non-Hodgkin lymphomas in developed countries, and a higher percentage in developing countries; older people are prone to the disease. Three frequent morphological variants have been recognized, including centroblastic, immunoblastic, and anaplastic variants. However, there are still other rare morphological variants of DLBCL, presenting challenge in diagnosis and treatment.
METHODS: A 62-year-old woman sought medical attention with a previous 6-month history of intermittent fever and leukocytosis. Bone marrow (BM) aspiration presented AML with acute monocytic leukemia-like morphologic features. The results of the immunophenotypic analysis suggested mature B cell lymphoma without obvious subtype characteristics. Lymph node biopsy indicated DLBCL of non-germinal centre B-cell subtype (n-GCB). Cytogenetic analysis of the BM cells revealed a 46,XX, trp(1)(q21q32),del(7)(q32q36),t(9;14)(p13;q32) [4]/46,XX [16] karyotype. The patient was diagnosed with EBV-positive DLBCL, NOS based on the combination of lymph node biopsy, clinical, cytological, immunophenotypic, and cytogenetic analyses.
CONCLUSIONS: To date, no case reports of a patient diagnosed with DLBCL mimicking acute monocytic leukemia with complex karyotype have been reported. We present the case given its rarity, easy misdiagnosis, and poor prognosis. The case highlights the importance of awareness about the rare morphological variant to laboratory staff and hematologists.

Objective: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . Methods: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. Results: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5-8, 4 in the DNA binding domain of exon 3-4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26-72) years old vs 45 (14-75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs 6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78-21.42) months vs 31.4 (95%CI 13.20-49.59) months, P=0.029]. The OS of patients treated with \"Decitabine + CAG\" was superior than that of patients treated with \"3 + 7\" regimen [30.0 (95%CI 27.35-38.84) months vs 12.5 (95%CI 5.80-19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. Conclusion: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.
目的： 探讨伴TP53基因异常急性髓系白血病（AML）患者的临床特征及预后。 方法： 回顾性分析2010年1月至2019年1月上海长海医院血液科新诊断的有初发靶向二代测序（NGS）数据的265例AML患者临床资料。采用包含210个血液肿瘤相关基因的靶向测序技术进行突变分析。分析TP53基因突变和（或）缺失与临床特征之间的关系及其对患者生存的影响。 结果： 20例（7.5%）患者伴TP53基因异常，其中错义突变17例（6.4%），移码（缺失）基因突变2例（0.7%），剪切位点突变1例（0.4%）。共检测到23种TP53基因突变，其中4个位于DNA结合结构域第3~4号外显子，16个位于DNA结合结构域第5~8号外显子，2个位于第10号外显子，1个为剪切子突变。伴TP53基因异常患者平均突变基因个数（6.2个）与无TP53基因异常组（6.4个）差异无统计学意义（P=0.770）。TP53基因异常患者的中位年龄为52（26~72）岁，高于无TP53基因异常患者的45（14~75）岁（P=0.008）；复杂核型比例（45.0%，9/20）显著高于无TP53异常组（6.1%，15/245）（P<0.001）；中位总生存（OS）时间[14.1（95%CI 6.78~21.42）个月]较无TP53异常组[31.4（95%CI 13.20~49.59）个月]显著缩短（P=0.029）。20例伴TP53基因异常患者中4例采用\"地西他滨+CAG\"方案诱导治疗，15例采用\"3+7\"方案治疗，中位生存时间分别为30.0个月和12.5个月（P=0.018）。多因素分析中，TP53、DNMT3A、USH2A基因异常及初发WBC>12.45×10(9)/L是影响OS的独立预后不良因素。 结论： 伴TP53基因异常AML患者中错义突变常见，突变位点主要分布于DNA结合结构域。TP53基因异常与高龄、复杂核型相关，且常与多个基因突变相伴出现。以地西他滨为基础的诱导化疗及异基因造血干细胞移植可能会提高患者生存率。.

Objective: To analyze the survival and first-line immune-chemotherapy (CIT) of chronic lymphocytic leukemia (CLL) with abnormal TP53 gene in the era of traditional CIT. Methods: The clinical data of 118 CLL patients diagnosed from January 2003 to August 2017 were collected. Survival was analyzed according to indicators including sex, age, Binet risk stratification, B symptoms, β(2)-microglobulin (β(2)-MG) , immunoglobulin heavy chain variable region gene (IGHV) mutation status, chromosome karyotype and TP53 gene deletion/mutation. The efficacy of first-line CIT of 101 CLL patients was further analyzed. Results: Among 118 patients, median progression-free survival (PFS) was 12 (95%CI 10.148-13.852) months and median overall survival (OS) was 53 (95%CI 41.822-64.178) months, only 30.5% patients survived over 5 years. Low β(2)-MG<3.5 mg/L indicated longer PFS (P=0.027) , female and Binet A patients had longer OS (P=0.011 and 0.013, respectively) . Of 118 patients, 17 (14.4%) didn\'t receive any therapy until follow-up time or the dead time. Among the 101 patients who received ≥1 CIT, median time to first treatment (TTFT) was 1 (0-62) months, patients in Binet A had longer TTFT (P<0.001) compared to the patients in Binet B/C. According to statistical needs, we divided those first-line CIT into four groups: there were 30 cases (29.7%) in mild chemotherapy group (mainly treated with nitrogen mustard phenylbutyrate or rituximab alone) , 32 cases (31.7%) in the fludarabine-containing group, 23 cases (22.8%) in high-dose methyprednisolone (HDMP) containing group and 16 cases (15.8%) in the other chemotherapy group. The first regimen contained HDMP can bring longer PFS (P<0.001) , however the OS between four groups had no statistical differences. Conclusion: CLL patients with abnormal TP53 gene had poor response to immunotherapy, rapid clinical progressing, first-line immunotherapy containing HDMP can prolong PFS and will create an opportunity for patients to participate in clinical trials of novel drugs.
目的： 分析传统免疫化疗（CIT）时代，TP53基因异常[TP53缺失和（或）突变]慢性淋巴细胞白血病（CLL）患者一线CIT疗效及生存情况。 方法： 收集2003年1月至2017年8月在江苏省人民医院血液科诊断的118例TP53异常CLL患者基线资料[性别、年龄、分期、B症状（发热、盗汗、体重减低）、β(2)微球蛋白（β(2)-MG）、免疫球蛋白重链可变区（IGHV）突变状态、染色体核型、一线CIT]进行生存分析，分析101例接受一线CIT患者的疗效。 结果： 118例CLL患者均通过电话、门诊及住院等方式随访至2018年3月10日，中位无进展生存（PFS）时间为12（95%CI 10.148~13.852）个月，中位总生存（OS）时间为53（95%CI 41.822~64.178）个月。分析患者基线资料对患者生存影响，β(2)-MG<3.5 mg/L患者具有较长的PFS时间（P=0.027），女性患者以及Binet A期患者具有更长OS时间（P=0.011）。118例患者中，有17例（14.4%）自诊断至死亡/随访终点未接受任何抗肿瘤治疗，101例接受了一线及以上的CIT（85.6%），中位至首次治疗时间（TTFT）仅为1（0~62）个月，Binet A期较Binet B/C期患者具有更长TTFT（P<0.001）。进一步分析101例患者初治方案，按治疗方案分为四组，分别是温和治疗组（主要为单用苯丁酸氮芥或单用利妥昔单抗治疗）30例（29.7%），含氟达拉滨化疗组32例（31.7%），含大剂量激素化疗组23例（22.8%），其他化疗组16例（15.8%）。含大剂量激素化疗方案可获得较长PFS时间（P<0.001），四组间OS差异无统计学意义。 结论： TP53基因异常的CLL患者对免疫化疗反应差，临床进展迅速，一线使用含大剂量激素方案化疗可以延长PFS时间，为患者后续加入复发难治新药临床试验创造机会。.

UNASSIGNED: Although contemporary chemotherapy has improved the cure rate of childhood acute lymphoblastic leukemia (ALL) to nearly 90%, relapsed/refractory ALL is still a leading cause of tumor-related death in children. To clarify the underlying mechanisms of relapsed/refractory childhood ALL, researchers urgently need to establish novel cell models from patients with relapsed ALL after treatment with contemporary chemotherapy.
UNASSIGNED: Cell culture technique was used to establish the HXEX-ALL1 cell line from primary B cell precursor ALL (BCP-ALL) cells. Molecular and cellular biological techniques including flow cytometry, polymerase chain reaction (PCR), short tandem repeat (STR) analysis, conventional cytogenetics, and chromosomal microarray analysis (CMA) were used to characterize the HXEX-ALL1 cell line. Nude mice were used for xenograft studies.
UNASSIGNED: A stable ALL cell line, HXEX-ALL1, derived from a 6-year-old boy of Han nationality with BCP-ALL at the second relapse, was established and maintained in culture for more than 18 months. The HXEX-ALL1 cell line was authenticated as being derived from primary leukemia cells based on morphologic, immunophenotypic, cytogenetic and STR analyses and demonstrated tumorigenicity in nude mice. WGS data showed that there were 27,006 novel single nucleotide polymorphisms (SNPs) and 193,951 novel insertion/deletions (InDels) in HXEX-ALL1 cells. Compared with the other BCP-ALL cell lines in use, the HXEX-ALL1 cells have a special karyotype represented by trisomy 8 and 9p and 17p deletions with a multidrug resistance phenotype, especially highly resistant to asparaginase.
UNASSIGNED: The HXEX-ALL1 cell line may prove to be a useful model for the study of relapsed/refractory childhood ALL, particularly for the researches on asparaginase resistance.

We retrospectively analyzed 101 primary MDS patients with complex karyotype during January 2010 and April 2017.The median overall survival (OS) time was 13 (95% CI 9.98-16.02) months, and there was no significant difference in OS for different treatment. Chromosome 5/7 involvement was common (78.22%, 79/101) and associated with shorter OS (12 months vs. 28 months, P < 0.01) Monosomal karyotype (MK) is overlapped with CK in 79 patients, but was not statistically associated with shorter OS. While in 59 cases with genes sequenced, 57 (96.61%) patients were found to have at least one mutation of known significance, and TP53 was the most frequent (74.58%, 44/59), the median OS of patients with TP53 mutation was shorter than those without (10 vs. 27 months, P < 0.01). Multivariate analysis demonstrated that only TP53 mutation was the strongest independent prognostic factor for OS. Moreover, high variant allele frequency (VAF) of TP53 mutation (median VAF was 70.00%) was seen and associated with adverse survival (9 months vs. 13 months, p = 0.04). In conclusion, MDS patients with CK implied an unfavorable outcome regardless of any treatment, TP53 mutation occurs at a high frequency and has a higher VAF, both were associated with worse survival.