Spectral karyotyping and fluorescence in situ hybridization detect novel chromosomal aberrations, a recurring involvement of chromosome 21 and amplification of the MYC oncogene in acute myeloid leukaemia M2

Recurring chromosomal aberrations are of aetiological, diagnostic, prognostic and therapeutic importance in acute myeloid leukaemia (AML). However, aberrations are detected in only two thirds of AML cases at diagnosis and recurrent balanced translocations in only 50%. Spectral karyotyping (SKY) enables simultaneous visualization of all human chromosomes in different colours, facilitating the comprehensive evaluation of chromosomal abnormalities. Therefore, SKY was used to characterize 37 cases of newly diagnosed AML-M2, previously analysed using G-banding. In 15/23 patients it was possible to obtain metaphases from viably frozen cells; in 22 additional cases, fixed-cell suspensions were used. Of the 70 chromosomal aberrations identified by SKY, 30 aberrations were detected for the first time, 18 aberrations were redefined and 22 were confirmed. SKY detected two reciprocal translocations, t(X;3) and t(11;19). In five cases, eight structural aberrations resulted in partial gains of chromosome 21, six of which were undetected by G-banding. In 4/5 cases, these resulted in copy number increases for AML1. Amplification of MYC was detected in three cases. Using SKY and FISH, clonal aberrations were identified in 5/18 cases with a presumed normal karyotype; 3/5 aberrations were of known unfavourable prognostic significance. Karyotypes were entered into a custom-designed SKY database, which will be integrated with other cytogenetic and genomic databases.     

Comparison between interphase and metaphase cytogenetics in detecting chromosome 7 defects in hematological neoplasias

Monosomy 7 (–7) is one of the most common chromosomal abnormalities found in the leukemic cells of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Because patients with –7 have a poor prognosis, their identification is important for treatment planning. Conventionally, –7 is detected by the G-banding technique. This study examines the use of fluorescent in situ hybridization (FISH) methodology to detect –7 cells in interphase nuclei and metaphase chromosomes. Fifteen AML or MDS patients whose leukemic cells were found to have –7 by G-banding at disease presentation were studied. In 13 of these patients, –7 could be detected in interphase by FISH using a chromosome 7-specific centromeric DNA probe. The two patients whose leukemic cells were not detectable by interphase FISH had –7 and t(1q;7p), which were detectable by FISH in metaphase using a chromosome 7-specific painting probe. Metaphase FISH was particularly useful in further defining chromosome 7 defects in cells that contained aberrant or marker chromosomes. For example, in 6 patients, chromosome 7 sequences were detectable in aberrant or marker chromosomes by metaphase FISH, but not by G-banding. These results suggest that metaphase FISH is an important adjunct to conventional cytogenetic methods for defining chromosome 7 abnormalities in AML and MDS patients. Furthermore, interphase FISH is useful for follow-up studies in patients who are found informative for the FISH study at presentation.     

Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients

Diffuse large B-cell lymphoma (DLBCL), a histologically well-defined subset of non-Hodgkin lymphoma, is clinically and genetically heterogenous. By G-banding, most cases showed complex hyperdiploid karyotypes and diverse cytogenetic abnormalities that included recurring and nonrecurring translocations, deletions, duplications, and marker chromosomes. While G-banding provided valuable leads to identification of specific rearrangements that enabled gene discovery and clinical correlations, many aberrations remained uncharacterized because of their complexity. The molecular cytogenetic technique spectral karyotyping (SKY), on the other hand, enables complete characterization of all aberrations in a tumor cell karyotype and, hence, precise quantitation of chromosome instability. We report here, for the first time, SKY analysis of a panel of 46 DLBCL cases previously analyzed by G-banding, ascertained at the Memorial Sloan-Kettering Cancer Center. This analysis provided a cytogenetic profile of DLBCL that was characterized by a higher level of instability, qualitatively as well as quantitatively, compared with G-banding. Thus, 551 breakpoints were detected by SKY, in contrast to the 295 by G-banding. Several new recurring breakpoints, translocations, and regions of gain and loss were identified, which included 13 breakpoints not previously identified by G-banding, 10 breakpoints that were underrepresented by G-banding, and 4 previously unrecognized translocations: der(14)t(3;14)(q21;q32), t(1;13)(p32;q14), t(1;7)(q21;q22), and der(6)t(6;8)(q11;q11). We identified new clinical associations involving recurring breakpoints detected by SKY. These studies emphasize the value of SKY analysis for redefinition of chromosomal instability in DLBCL to enhance gene discovery as well as clinical correlation analysis.     

Interphase fluorescence in situ hybridization and spectral karyotyping reveals hidden genetic aberrations in children with acute lymphoblastic leukaemia and a normal banded karyotype

Twenty-two cases of childhood acute lymphoblastic leukaemia (ALL) with normal G- or Q-banded karyotypes were studied by interphase fluorescence in situ hybridization (FISH) and spectral karyotyping. Probes detecting MLL, BCR/ABL and TEL/AML1 rearrangements were used for the interphase studies, along with centromere-specific probes from chromosomes 17 and X. In 10 patients (45%), previously undetected aberrations were demonstrable. Specific gene rearrangements and structural changes were found in six cases and numerical changes in five. Five of these aberrations have previously been reported to have an impact on prognosis. Three cases were massively hyperdiploid and, in one, the prognostically important BCR/ABL fusion was detected. In addition, a near-haploid karyotype with 27 chromosomes was found in one patient and TEL/AML1 rearrangements were detected in two cases. This study indicates that about half of childhood ALL cases with apparently normal karyotypes harbour genetic aberrations that may be detected using interphase FISH and spectral karyotyping.     

Frequency and prognostic value of chromosome abnormalities in multiple myeloma

Chromosomal aberrations have been shown to significantly affect survival in multiple myeloma (MM), but few cytogenetic analyses among Japanese MM patients have been reported. Using a commercial laboratory, we performed interphase fluorescent in situ hybridization (FISH), as well as a conventional metaphase cytogenetic study (G-banding), among 106 of 131 patients between April 1997 and February 2007. Karyotype abnormalities were found in 21.2% (21 of 99 patients). Del(13q), del(17p), del(11q), t(11;14) and t(4;14) were detected by FISH in 36.0% (31/86), 24.7% (19/77), 7.6% (5/64), 18.2% (12/66) and 10.4% (7/67) of patients, respectively. The prevalence of abnormalities detected by G-banding was lower than that reported in European countries, but when compared with FISH studies, no difference was observed. Prognostic analyses of patients with these abnormal chromosomes revealed that those with abnormal karyotype and del(13q), t(4;14), as detected by FISH, had significantly poorer survival. This study suggests that the prevalence of chromosome abnormalities among Japanese patients is similar to that for European populations, and that chromosome studies by G-banding and FISH are essential to predict survival.     

Cytogenetics of multiple myeloma: interpretation of fluorescence in situ hybridization results

The cytogenetic picture in multiple myeloma (MM) is highly complex, from which non-random numerical and structural chromosomal changes have been identified. Specifically, translocations involving the immunoglobulin heavy chain gene (IGH) at 14q32 and either monosomy or deletions of chromosome 13 have been reported in a significant number of patients from both cytogenetic and interphase fluorescence in situ hybridization (FISH) studies. Importantly, these abnormalities of chromosome 13 have recently been associated with a poor prognosis. In view of the highly complex nature of the karyotypes in MM patients, interphase FISH results may be difficult to interpret. In this study, cytogenetics and/or interphase FISH were carried out on bone marrow samples or purified plasma cells from 37 MM patients. Abnormal karyotypes, characterized by multiplex FISH (M-FISH) were found in 11 patients, all of which were highly complex. Interphase FISH revealed translocations involving the IGH locus in 16 (43%) patients. The IGH/cyclin D1 (CCND1) gene fusion characteristic of the translocation, t(11;14)(q13;q32), was seen in 12 (32%) of these patients and other rearrangements of IGH in four (11%) patients. Fourteen patients had additional copies of chromosome 11. Twenty patients (54%) had 13q14 deletions, 10 of whom also had t(11;14) or another IGH translocation. By comparing cytogenetic and FISH results, this study has revealed that significant chromosomal abnormalities might be hidden within highly complex karyotypes. Therefore, extreme caution is required in the interpretation of interphase FISH results in MM, particularly in relation to certain abnormalities, such as 13q14 deletions, which have an impact on prognosis.     

Design and validation of DNA probe sets for a comprehensive interphase cytogenetic analysis of acute myeloid leukemia

The objective of this study was to design DNA probe sets that enable the detection of chromosome aberrations in acute myeloid leukemia (AML) by interphase cytogenetics using fluorescence in situ hybridization (FISH) and to compare the results of interphase cytogenetics with those of conventional chromosome banding analysis. One hundred five consecutive patients with adult AML entered on a multicenter treatment trial were studied with a comprehensive set of DNA probes recognizing the most relevant AML-associated structural and numerical chromosome aberrations: translocations t(8;21), t(15;17), and t(11q23); inversion inv(16);chromosomal deletions (5q-, 7q-, 9q-, 12p-, 13q-, 17p-, and 20q- ); and chromosomal aneuploidies. Interphase cytogenetics was particularly sensitive for detecting the AML-specific gene fusions: 3 additional cases of inv(16) and 1 additional case of t(8;21) were identified by FISH that were missed by banding analysis, whereas equal numbers of t(11q23) and t(15;17) were detected. Five additional cases of trisomy 8q, 3 more cases of trisomy 11q, and 2 more cases of trisomies 21q and 22q were shown by FISH. These aberrations were either masked in complex karyo-types or identified in cases in which conventional banding analysis failed. On the other hand, the DNA probes selected were not informative to detect 1 case of 5q-, 9q-, and 20q-. In 5 cases, clonal aberrations were detected on banding analysis for which no FISH probes were selected. In conclusion, interphase cytogenetics proved to be more sensitive for detecting AML-specific chimeric gene fusions and some partial trisomies. Interphase cytogenetics provides a powerful technique complementary and, with further development of diagnostic DNA probes, even an alternative to chromosome banding studies for the cytogenetic analysis of AML.     

Interphase Fluorescence In Situ Hybridization Detection of Cytogenetic Abnormalities in B-Cell Chronic Lymphocytic Leukemia

The most frequent chromosomal abnormalities in B-cell chronic lymphocytic leukemia (B-CLL) are deletions on 13q14 and 17p13, trisomy 12, and 14q32 rearrangement. Conventional cytogenetic analysis underestimates the frequency of specific chromosome aberrations in B-CLL because of the low rate of spontaneous mitoses and the poor response to mitogen stimulation. We used interphase fluorescence in situ hybridization (I-FISH) to explore the incidence of chromosomal changes in the peripheral blood cells of B-CLL patients. Probes for 13q14 (D13S319), 17p13 (p53), the centromere of chromosome 12 (CEP12), and 14q32 (IGHC/IGHV) were applied to detect chromosomal aberrations in peripheral blood samples from 83 B-CLL patients (60 men, 23 women). Molecular cytogenetic aberrations were found in 61 cases (73.5%), and 8 patients (9.6%) showed 2 kinds of abnormalities. The most frequent abnormality was deletion of 13q14 (41.0%), followed by +12 (19.3%), deletion of 17p13 (12%), and 14q32 rearrangement (9.6%). FISH results were analyzed for correlation with Binet stages. The percentages of patients who showed abnormalities by FISH were 73.0%, 73.3%, and 80% for Binet stages A, B, and C, respectively, and the percentages of patients with abnormalities who showed 2 anomalies were 7.9%, 27.3%, and 0% for Binet stages A, B, and C, respectively. We noted no consistent pattern among the various Binet stages in the distribution of either the types of FISH-detected anomalies or the numbers of FISH anomalies. I-FISH was found to be a rapid, exact, and sensitive technique for analysis of chromosome aberrations in CLL. FISH could provide accurate information regarding the molecular cytogenetic features of CLL.     

A Retrospective Analysis of Cytogenetic and Clinical Characteristics in Patients With Multiple Myeloma

BackgroundCytogenetic alterations in patients with multiple myeloma (MM) represent important risk factors in terms of prognosis. In this study, the impact of the cytogenetic aberrations of MM on patient clinical features and outcome was investigated.MethodsConventional cytogenetic analysis with R-banding technique and molecular cytogenetic characterization by interphase fluorescence in situ hybridization (FISH) were used to detect aberrant chromosomal arrangements, including 17p13 and 13q14 deletions, 14q32 rearrangement and 1q21 amplification, in bone marrow nucleated cells from 65 patients.ResultsAbout 16.9% of patients showed aberrations by conventional cytogenetic analysis, whereas 49.2% of patients showed aberrations by interphase FISH analysis. Abnormalities of 13q14, 1q21, 14q32 and 17p13 were detected in 27.7%, 13.8%, 16.9% and 29.2%, respectively. Patients with a 13q14 deletion or combined with 17p13 deletion frequently had a late stage of the disease, and tended to have elevated serum levels of β₂ microglobulin and lower levels of albumin. The progression-free survival and overall survival of FISH-positive patients were lower than for those without detectable abnormalities, especially in the conventional chemotherapy arm.ConclusionsThese findings demonstrate that myeloma cells are prone to exhibiting a complex aberration and that FISH is superior to conventional cytogenetic analysis with a higher detection rate of chromosomal abnormalities. Patients with a 17p13 or 13q14 deletion, 14q32 rearrangement and 1q21 amplification were more likely to have a poor prognosis for MM.     

Molecular cytogenetic aberrations in 21 Chinese patients with plasma cell leukemia

Plasma cell leukemia (PCL) is a rare malignant plasma cell disorder. Cytogenetic studies performed on plasma cell disorders are scarce and difficult because of the low proliferation rate of plasma cells (PCs). Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of chromosomal changes in PCL. To explore the molecular cytogenetic abnormalities in Chinese patients with PCL, interphase FISH studies with three probes for the regions containing 13q14.3 (D13S319), 14q32 (IGHC/IGHV) and 1q12(CEP1) were retrospectively performed in 21 PCL patients. FISH with LSI IGH/CCND1 and LSI IGH/FGFR3 probes were used to detect t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with 14q32 rearrangement. Among 21 PCL patients, molecular cytogenetic aberrations were found in 18 (81.8%) patients, four (19.0%) patients simultaneously had 13q14 deletion, illegitimate IgH translocation and 1q abnormality. 13q14 deletion was detected in 13 (61.9%) cases and illegitimate 14q32 rearrangement in 16 (76.2%) including six with t(11;14) and three with t(4;14). Chromosome 1 abnormality was found in seven (33.3%) patients, one with deletion of 1q, six with at least three copies amplifications of 1q12 (Amp1q12). 14q32 rearrangement and 13q14 deletion were found concurrently in 11 (52.4%) cases. It was showed that most PCL had chromosomal abnormalities, 14q32 rearrangement, 13q14 deletion and chromosome 1 abnormality are the frequent abnormalities, and over half of the 14q32 rearrangement were t(11;14) or t(4;14). t(4;14) and 13q14 deletion were correlated in PCL. FISH is a highly sensitive technique at detecting molecular cytogenetic aberrations in PCL and should be used in the routine evaluation of PCL.     

Numerical gain and structural rearrangements of JAK2, identified by FISH, characterize both JAK2617V>F-positive and -negative patients with Ph-negative MPD, myelodysplasia, and B-lymphoid neoplasms

OBJECTIVE: Current evidence suggests that the JAK2617V>F point mutation is implicated in the pathogenesis of >90% of polycythemia vera (PV) patients, and in approximately 50% of primary myelofibrosis (PMF) and essential thrombocythemia patients. Novel JAK2 mutations were recently described in 5% to 15% of patients that are JAK2617V>F-negative. Additionally, JAK2 is reported to form fusion hybrids with three different genes. We, therefore, hypothesized that patients with 9p24 chromosomal rearrangements or patients with Philadelphia chromosome (Ph)-negative myeloproliferative disorders (MPDs), with or without +9/+9p chromosomal abnormalities, might demonstrate additional and/or cryptic JAK2 structural rearrangements. METHODS: Metaphase and interphase cells were retrospectively investigated from 39 patients using two JAK2 BAC fluorescence in situ hybridization (FISH) probes on archived fixed cell suspensions. Of the 39 patients, 8 had PV with chromosome 9 abnormalities, 7 had PMF/MPD showing an abnormal karyotype, 10 PV patients were cytogenetically normal, and 14 patients had 9p24 chromosomal abnormalities. RESULTS: FISH studies revealed 11 JAK2617V>F-positive patients with JAK2 numerical and structural abnormalities. Trisomy through hexasomy as well as JAK2 amplification (15-20 copies) was observed in nine patients (PV, 6; non-Hodgkin lymphoma [NHL], 1; multiple myeloma, 1; and MDS, 1), while JAK2 structural abnormalities were seen in two patients (MDS and NHL). Among the seven patients negative for JAK2617V>F mutation, two patients with MDS were observed with JAK2 rearrangements involving NF-E2 and AML1. The status of JAK2617V>F mutation could not be determined in 13 patients, but FISH studies revealed both gain and rearrangements in three patients. They include one patient with PV and +9p with three copies of JAK2 and two patients with MDS and JAK2 relocations: one with NF-E2, while the other patient with a TEL/ETV6 rearrangements also had tetrasomy for JAK2. CONCLUSION: JAK2 FISH studies revealed two types of JAK2 rearrangements among patients with Ph-negative MPDs and non-MPDs: gain and/or structural rearrangements. Gain and amplification of JAK2 was primarily observed in patients that were JAK2617V>F-positive (9 of 11), irrespective of the diagnosis, while rearrangements of JAK2 were frequently seen in patients who lacked the JAK2617V>F mutation with either MDS or AML (5 of 6). Three different JAK2 abnormalities were identified in one clone for the first time in two patients with PV. The data also identified a myriad of JAK2 rearrangements, including a novel JAK2-NF-E2 interaction, JAK2 translocation to chromosomes 3, 4, 12, 14, and 21 and detection of the previously described rare TEL/ETV6-JAK2 translocation. These observations suggest that JAK2 attracts multiple gene partners and may contribute to disease progression in patients with MDS and B-cell malignancies, while the JAK2 copy number appears to be important in pathogenesis of Ph-negative MPDs.     

Chromosome aberrations in de novo acute myeloid leukemia patients in Kuwait

Cytogenetic analysis was successfully performed at the time of diagnosis in 45 patients with de novo acute myeloid leukemia, including 10 children and 35 adults. In approximately 73% of AML patients (35 patients) clonal chromosome abnormalities were detected at the time of diagnosis. Twelve patients (22.8%) had apparently normal karyotypes. Recurring aberrations found in 22 of patients with abnormal karyotypes included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), trisomy 8, monosomy 7 and del(5q). The highest frequency of chromosome changes was observed in AML-M3. The occurrence of the classical cytogenetic abnormalities was not a ubiquitous phenomenon. In 11 patients previously not described miscellaneous clonal chromosomal abnormalities were detected. Clonal chromosomal abnormalities detected in AML have shown correlations between specific recurrent chromosomal abnormalities and clinico-biological characteristics of the patients, therefore have been repeatedly shown to constitute markers of diagnostic and prognostic significance. Moreover, ongoing cytogenetic analysis can identify new nonrandom chromosome aberrations in AML and contribute to the identification of novel genes involved in the development of cancer, which can lead to better understanding of the disease pathogenesis.     

Efficacy of high-resolution comparative genomic hybridization (HR-CGH) in detection of chromosomal abnormalities in children with acute leukaemia

The efficient detection of chromosomal aberrations in childhood acute leukaemias presents a significant component in the diagnostics of this frequent malignant disease. We used comparative genomic hybridization (CGH) and high-resolution comparative genomic hybridization (HR-CGH) to determine the frequency of chromosomal changes in 33 children with acute leukaemia (AL). The yields of chromosomal abnormalities were compared with the results obtained using conventional cytogenetics (G-banding) and fluorescence in situ hybridization (FISH). Conventional cytogenetics revealed chromosomal changes in 17 (52 %) of studied patients. The employment of FISH together with G-banding analysis identified chromosomal changes in 27 (82 %) of the AL patients investigated. CGH detected changes in DNA copy numbers in 24 (73 %) patients, 40 losses and 67 gains were found in total. HR-CGH disclosed 98 losses and 97 gains in 26 (79 %) patients. In comparison with CGH, HR-CGH analyses unveiled 88 new chromosomal aberrations: 58 losses and 30 gains. The most commonly gained chromosomes were 21 (22.5 %), X (15 %), 18 (12,5 %) and 17 (10 %). The most common losses involved sub-regions or arms of chromosomes 7 (15 %), 9 (12.5 %), 16, 19 and 1 (10 % each). Cytogenetic and molecular cytogenetic analyses of 33 childhood acute leukaemias revealed chromosomal changes in total 31 (94 %) patients. The evaluation of HR-CGH sensitivity proved that the minimal cell population of malignant cells in which a certain chromosomal change could be found was close to the 20 - 30 % level. Our results confirm the benefits of HR-CGH in detecting chromosomal changes in childhood AL. Supplementing G-banding and FISH with the HR-CGH diagnostic method increases the detection of unbalanced structural chromosomal rearrangements and can reveal small cell clones with gains and losses of whole chromosomes in hyperdiploid AL.     

Co-existence of multiple subclones in TEL-AML1 at diagnosis of acute lymphoblastic leukaemia in association with submicroscopic deletion of AML1

The TEL/AML1 (ETV6/RUNX1) fusion gene is the most common genetic rearrangement in paediatric acute lymphoblastic leukaemia (ALL). Although considered to be a low-risk leukaemia, it is associated with a relapse rate of 10-20%. The coexistence of different subclones at diagnosis, based on polymerase chain reaction (PCR) studies of IG/TCR gene rearrangement, with differential response to chemotherapy, was recently reported in this subtype of ALL. We wished to demonstrate such subclones at diagnosis by a recently developed technique of quantitative multiparametric fluorescence in situ hybridization (FISH). Bone marrow cells from 80 paediatric patients with ALL at diagnosis were analysed for the presence of the TEL/AML1 fusion gene by interphase FISH. Fourteen patients were positive for the translocation. Four of them had several subclones associated with various combinations of additional chromosomal abnormalities. The most striking was an atypical and unexpected hybridization pattern consistent with a submicroscopic deletion of the 5' region of the AML1 breakpoint. Other abnormalities included TEL deletion, trisomy and tetrasomy 21 as well as double TEL-AML1 fusion. The presence of numerous subclones in about 25% of patients with TEL/AML1+ ALL suggests extensive clonal evolution by the time of diagnosis.     

Acute lymphoblastic leukaemia: diagnosis and classification

Acute lymphoblastic leukaemia (ALL) is a heterogeneous disease with distinct biological and prognostic groupings. Diagnosis relies on traditional cytomorphological and immunohistochemical evaluation of the leukaemic blasts. Subsequently, cytogenetic analysis identifies clonal numeric and/or structural chromosomal abnormalities that may be present, thus confirming the subtype classification and providing important prognostic information for treatment planning. The major chromosomal abnormalities in ALL are t(9;22)(q34;q11), t(12;21)(p13;q22), t(4;11)(q21;q23), t(1;19)(q23;p13), 8q24 translocations and hyperdiploidy. Generally, hyperdiploidy, occurring most frequently in paediatric cases, is associated with a good prognosis, while hypodiploidy confers a poor prognosis. Among structural chromosomal abnormalities, the t(9;22)(q34;q11) resulting in the BCR/ABL fusion protein, and rearrangements of the MLL gene, confer a poor prognosis in both children and adults, while t(12;21)(p13;q22), resulting in the TEL/AML1 fusion protein, and del (12p) confer a good prognosis. More recently, additional diagnostic and prognostic information has been gained from fluorescence in situ hybridization (FISH) and DNA microarray techniques.     

急性髓性白血病178例患者的细胞遗传学特征

目的 探讨急性髓性白血病(AML)患者的细胞遗传学特征.方法 采用骨髓短期培养和G显带技术对178例AML患者进行染色体核型分析.结果 178例患者中,171例有足够可供分析的中期分裂象.171例患者异常克隆检出率74.9%.其中27例患者为骨髓增生异常综合征(MDS)继发AML,其异常克隆榆出率为92.6%,在其余144例原发AML中异常克隆检出率为71.5%,MDS继发AML异常克隆检出率明显高于原发AML患者.171例患者中预后良好核型占24.0%,预后中等核型占46.8%,预后不良核型占29.2%.在预后良好核型中以t(15;17)为多;在预后中等核型中以正常核型为主;在预后不良核型中以复杂异常核型为主,复杂核型的异常克隆中常含有-5/5q-、-7/7q-等具有不良预后的异常克隆.老年组75例患者中,预后良好、预后中等及预后不良核型分别为16.0%、48.0%及36.O%,年轻组96例患者中分别为30.2%、45.8%及24.0%.老年患者预后良好核型比例低于年轻患者.MDS继发AML患者预后不良核型比例及单体核型比例均高于原发AML患者(P值均<0.001).结论 t(15;17)、正常核型、复杂核型分别是AML最常见的预后良好核型、预后巾等核型及预后不良核型.MDS继发的AML及老年AML患者染色体核型预后不良.

Abstract：

Objective To explore the cytogenetic characteristics of acute myeloid leukemia(AML) patients.Methods The karyotype analysis was performed in 178 AML using the short-term culture of bone marrow cell and G-banding technique.Results Among the 178 patients,171 had enough metaphases for analysis and 128(74.9%)had clonal karyotypic abnormalities.Twenty-seven patients were secondary to myelodysplastic syndrome (MDS-AML),with 25 (92.6%) patients carrying clonal karyotypic abnormalities.Among the remaining 144 patients of de novo AML,103(71.5%)had clonal karyotypic abnormalities.The rate of abnormal clonal karyotype was higher in MDS-AML than that of de novo AML (P=0.021).Among the 171 patients,41(24.0%)were in favorable risk group,80(46.8%)in intermediate risk group and 50(29.2%)in adverse risk group.t(15;17)was the most common chromosomal aberration.The maiority intermediate risk chromosomal aberration was;normal karyotype.The most common cytogenetic abnormality among adverse group was a complex karyotype.Adverse cytogenetic aberrations,such as -5/5q-,-7/7q-,frequently occurred in conjunction with one another as part of a complex karyotype.Totally 75 patients were 60 years or older,among them,16.0%were in favorable risk group,48.0%in intermediate risk group and 36.0%in adverse risk group.Among 96 younger patients,30.2%were in favorable risk group.45.8%in intermediate risk group and 24.0%in adverse risk group.The rate of favorable risk chromosomal aberration was lower in elder patients than in younger(P=0.03 1).The rate of adverse risk chromosomal aberration and the rate of monosomal karyotype were higher in MDSAML than in de novo AML patients(P<0.001).Conclusions The most common favorable,intermediate and adverse chromosomal aberrations were t(15;17),normal karyotype and complex karyotype respectively.The karyotype was poor in MDS-AML and elder AML patients.     

Multicolour spectral karyotyping identifies new translocations and a recurring pathway for chromosome loss in multiple myeloma

Multicolour spectral karyotyping (SKY) was performed on primary tumour specimens from 100 patients with multiple myeloma (MM) that showed complex clonal chromosome aberrations not fully characterized by G-banding. In this study, SKY was able to identify or revise translocations with breakpoints involving 14q32, 11q13 or 8q24 in 32 patients (32%). Five new recurring translocations were identified, two of which involved chromosome 22. A subtle reciprocal translocation t(14;22) (q32;q11 approximately 12) was identified using SKY in two patients and a second, much larger, translocation t(11;22)(q13;q13) was identified using G-banding in three patients. A third new translocation was identified in two patients using SKY and G-banding as der(7)t(7;7)(p15 approximately 22;q22 approximately 32). Twenty-three patients (23%) showed the loss of 8p by whole-arm translocations with different whole-arm donor chromosomes. Among this group, two new recurring whole-arm translocations involving the centromeric breakpoint 8q10 were identified as der(8;20)(q10;q10) and der(8;18) (q10;q10) in three patients each. In addition, a novel pattern of three-way translocations involving the clonal evolution of the t(8;22)(q24;q11) by the subsequent loss of 8p by whole-arm translocations was found in three patients. The chromosome instability identified here demonstrates that the loss of 8p can occur by multiple whole-arm translocations, indicating a new pathway for the loss of a specific chromosome region in MM.