Chromosomal Aberrations in Peripheral Lymphocytes of Abstinent Alcoholics

The frequency of structural and/or numerical chromosomal aberrations in human metaphasic cells of lymphocyte cultures from abstinent alcoholics who were abstinent for 1 month up to 32 years was compared with those from controls not selected for alcohol consumption. Cytogenetic analyses revealed a significant increase of the frequencies of cells with structural aberrations in the abstinent alcoholics (7.1 %), compared with controls (2.4%). The frequency of numerical aberrations showed a significant regression on ages in abstinent alcoholics and controls. These results suggest specific action of chronic alcohol consumption impairing biological repair with aging. The increased frequency of chromosome-type aberrations associated with alcohol consumption, even after long withdrawal, could be due to an action of ethanol or its metabolites on primordial leukopoietic cells.     

Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic 46,XX,dup(9)(q22.3q34.1)/46,XX at amniocentesis in a pregnancy with a favorable outcome

ObjectiveWe present our observation of cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic dup(9)(q22.3q34.1) at amniocentesis in a pregnancy with a favorable outcome.Case reportA 37-year-old, gravida 4, para 0, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX, dup(9)(q22.3q34.1)[8]/46,XX[16]. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling, and repeat amniocentesis was performed at 21 weeks of gestation, which revealed a karyotype of 46,XX,dup(9)(q22.3q34.1)[7]/46,XX[25]. Simultaneous array comparative genomic hybridization (aCGH) on the DNA extracted from uncultured amniocytes revealed no genomic imbalance, or arr (1–22,X) × 2. Interphase fluorescence in situ hybridization (FISH) analysis on 105 uncultured amniocytes detected only one cell with the dup 9q signal with a mosaic dup 9q level of 1%, compared with 0% in normal control. At 37 weeks of gestation, a 2640-g female baby was delivered with no phenotypic abnormality. The cord blood had a karyotype of 46,XX,dup(9) (q22.3q34.1)[4]/46,XX[36], the umbilical cord had a karyotype of 46,XX,dup(9) (q22.3q34.1)[2]/46,XX[38], and the placenta had a karyotype of 46,XX. aCGH analysis on cord blood revealed no genomic imbalance. At age 2½ months, the baby was doing well, the peripheral blood of the baby had a karyotype of 46,XX,dup(9) (q22.3q34.1)[4]/46,XX[36], and interphase FISH analysis on buccal mucosal cells revealed no dup 9q signal in 100 buccal mucosal cells.ConclusionCytogenetic discrepancy may occur between cultured amniocytes and uncultured amniocytes in mosaic dup(9) (q22.3q34.1). Molecular cytogenetic analysis on uncultured amniocytes is useful for rapid distinguishing pseudomosaicism from true mosaicism under such a circumstance.     

Chromosome aberrations and cytogenetic intratumor heterogeneity in chondrosarcomas

Clonal chromosome aberrations identified after short-term culture are presented for 13 chondrosarcomas; in 5 cases both the primary tumors and local recurrences were studied. The stemline chromosome number was hypodiploid or hyperhaploid in 9 tumors. The most frequent numerical anomalies were, in falling order of frequency, loss of chromosomes Y, 10, 13, and 6, and gain of chromosomes 7 and 20. No recurrent structural rearrangement was found, but chromosome bands 5q13, 1q21, 7p11, and 20q11 were each involved in three different rearrangements. Karyotypic heterogeneity was assessed in two different ways: as the presence of more than one clone in one sample and as the presence of different clones in different samples from the same surgical specimen. Clonal karyotypic evolution was demonstrated in 6 of the 7 cases in which two or more samples could be investigated. All 6 showed intersample heterogeneity. Intrasample heterogeneity was found in only 5 of the 28 samples with aberrations. By comparing the incidences of the nonrandomly occurring aberrations in stemlines and sidelines in the heterogeneous tumors, it was possible to conclude that loss of chromosome 13 and rearrangement of band 5q13 were early events in the clonal evolution.Abbreviation EMC extraskeletal myxoid chondrosarcoma     

Subtypes of oligodendroglioma defined by 1p,19q deletions,differ in the proportion of apoptotic cells but not in replication-licensed non-proliferating cells

Oligodendrogliomas may be divided into those with deletion of chromosomes 1p and 19q (Del+), and those without (Del−). Del+ tumours show better survival and chemoresponsiveness but the reason for this difference is unknown. We have investigated whether these subgroups differ in (a) apoptotic index, (b) the proportion of cells licensed for DNA replication but not in-cycle, and (c) the relative length of G₁-phase. Fluorescence in situ hybridisation with probes to 1p and 19q was used to determine the deletion status of 54 oligodendrogliomas, including WHO grades II and III. The apoptotic index was determined using counts of apoptotic bodies. Replication-licensed non-proliferating cells were determined from the Mcm2 minus Ki67 labelling index, whilst the geminin to Ki67 ratio was used as a measure of the relative length of G₁. Del+ oligodendrogliomas showed a higher apoptotic index than Del− tumours (P = 0.037); this was not accounted for by differences in tumour grade or in proliferation. There were no differences in the Mcm2 − Ki67 index or in the geminin/Ki67 ratio between the subgroups, but grade III tumours showed a higher proportion of licensed non-proliferating cells than grade II tumours (P = 0.001). An increased susceptibility to apoptosis in oligodendrogliomas with 1p ± 19q deletion may be important in their improved clinical outcome compared to Del− tumours.     

眼镜蛇毒心脏毒素对人肺癌A_(549)细胞株的细胞遗传学效应

应用眼镜蛇毒心脏毒素（CT）处理体外培养的肺癌A549细胞株，通过细胞生长速率、有丝分裂指数（MI）、细胞周期动力学指数、SCE频率、二倍体细胞比率的分析，观察CT所产生的细胞遗传学效应。实验结果显示：CT能明显影响和抑制肺癌A543细胞的生长和增殖周期（P＜0．01），且随着浓度增大，癌细胞受抑制程度越大。用2μg／mlCT作用肺癌细胞后，SCE频率比对照组明显下降（P＜0．01），但对照组和实验组出现的二倍体细胞比率差异不明显（P＞0．05），提示CT可抑制肺癌细胞的恶性程度，但使其恶性表型逆转的作用不明显。     

多发性骨髓瘤生物学和临床诊治的新视野:第56届美国血液学会年会报道

多发性骨髓瘤(MM)是一种从癌前状态(意义不明的单克隆免疫球蛋白血症MGUS)到恶性疾病转化过程的独特肿瘤.在其发病过程中,肿瘤克隆的基因型特点与浆细胞与其微环境之间的对话同样重要.MM基因是高度复杂和异质性的,它们对疾病的转归起着关键的作用,不久以后MM可能将不再被视为一个单一的疾病.大量新药的应用,将增加对微小残留病监测预后和治疗效果的预期和需要.新药和高剂量化疗联合自体干细胞移植的应用使MM的预后已经在过去20年得到显著改善,重新审视早期MM的诊断标准和早期干预的可能性将开辟新的治疗途径.新药物的不断涌现,将促使人们平衡疗效、毒性和成本之间的关系,以达到最佳的治疗目标.     

Complete haematological and cytogenetic response to interferon alpha-2a of a myeloproliferative disorder with eosinophilia associated with a unique t(4;7) aberration

 A female patient with eosinophilia and cardiac symptoms was found to have a unique chromosomal aberration [t(4;7)(q11;p13)] of bone-marrow precursors. The disorder was classified as a chronic myeloproliferative syndrome with eosinophilia. Due to a significant increase in the white blood cell and eosinophil count during initial treatment with prednisone and hydroxyurea, Interferon alpha-2a was administered at a dose of 3–5×10⁶ I.U. s.c., five times per week, and induced a long-term complete haematological and cytogenetic response. The clinical features of this case are presented and discussed in the context of the current literature. Received: 26 June 1999 / Accepted: 3 September 1999     

Does myeloma genetic have an effect on stem cell mobilization?

BackgroundAutologous stem cell transplantation (ASCT) after induction treatment is the standard of care. Our understanding of myeloma genetics has been very limited and its effect to stem cell mobilization is not widely investigated. We aimed to investigate the effect of genetic abnormalities on stem cell mobilization in myeloma.MethodsThe data of 150 MM patients who underwent stem cell mobilization at our center between 2009–2020 were included and analyzed retrospectively. Pre-treatment bone marrow cytogenetics and fluorescence in situ hybridization tests were performed for each patient.ResultsGroups were divided into two as patients with normal cytogenetic and abnormal cytogenetic. No difference observed between groups regarding age, gender and ECOG (p = 0.4; p = 0.2; p = 0.3). Groups were similar concerning myeloma characteristics, received treatment and treatment response. Median CD34+ cells/kg harvested was 444(2−11.29) in normal cytogenetic group whereas it was 4,8(2.4−8.6) in abnormal cytogenetic group(p = 0.2). Optimal CD34+ cells level achievement was 73 (67 %) in normal cytogenetic group while it was 25(71.4 %) in abnormal cytogenetic group(p = 0.6). Neutrophil and platelet engraftment durations were similar among cytogenetic groups (p = 0.7; p = 0.9). R-ISS based groups were also did not differ regarding harvested CD34+ cells and achievement optimal CD34 level (p = 0.79, p = 0.74). Engraftment durations for neutrophil and platelet were comparable between R-ISS based groups (p = 0.59, p = 0.65)ConclusionsHere we were not able to find any impact of genetic abnormalities on stem cell mobilization in myeloma patients. Expanded studies can aid to identify the effect of particular genetic anomalies on the stem cell mobilization.