Does supplemental interphase FISH analysis to standard chromosom analysis improve the detection of myelodysplastic syndrome?

7060 Background: Our objective was to evaluate whether the addition of interphase FISH analysis to standard chromosome analysis (CA) improves the detection of chromosomal abnormalities in patients with work up for myelodysplastic syndromes (MDS), acute myeloid leukemia, and myelodysplastic/myeloproliferative disorders and thereby increases diagnostic and prognostic information. We performed a retrospective data review of all MDS orders between January and September 2015 at our institution and evaluated concurrent tests for discrepancies between CA and FISH results. Our aim was to evaluate best practices with regard to diagnostic test utilization, specifically to assess the diagnostic and prognostic value of FISH in addition to CA for patients with potential and known MDS. Methods: Retrospective data review of concurrent test orders of CA and myelodysplastic FISH panel were reviewed. The myelodysplastic FISH panel consists of screening for monosomy 5/deletion 5q, monosomy 7/deletion 7q, CEP7, trisomy 8, and D20S108 (20q12). The results of CA and FISH results were analyzed using a chi-square test to evaluate statistical significance. Results: A total of 1121 samples were queried, of which 55 were excluded due to inability to perform CA and limited diagnostic value of accompanying standalone FISH data on the 4 markers tested in this study. Analysis of the eligible 1066 samples showed that the standalone CA had significantly higher sensitivity (p < 0.0001) in detecting abnormal cases (N = 247, 23.17%) as compared to standalone FISH analysis (N = 180, 16.89%). Overall, 173 (16.23%) cases were determined to be abnormal by both methods. CA correctly interpreted 1059 of 1066 cases (99.34%).Only 7 samples were interpreted as normal by CA but were found to be abnormal by FISH. This results in overall 0.66% (2.76% of the abnormal cases) of abnormalities that would have been missed by CA only. Conclusions: These findings suggest that FISH studies with 4 markers used in this study provide limited additional utility in cases with a complete CA.

Download Full-text

Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis

European Journal of Human Genetics ◽

10.1038/sj.ejhg.5201178 ◽

2004 ◽

Vol 12 (7) ◽

pp. 513-520 ◽

Cited By ~ 40

Author(s):

Igor N Lebedev ◽

Nadezhda V Ostroverkhova ◽

Tatyana V Nikitina ◽

Natalia N Sukhanova ◽

Sergey A Nazarenko

Keyword(s):

Cell Culture ◽

Spontaneous Abortion ◽

Chromosomal Abnormalities ◽

Fish Analysis ◽

Interphase Fish

Download Full-text

Coexistance of Multiple Myeloma and Myelodysplastic Syndrome or Lymphoid Diseases At Diagnosis: Evidence for Two Clonal and Independent Chromose Abnormalities

Blood ◽

10.1182/blood.v118.21.5063.5063 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5063-5063

Author(s):

Hossein Mossafa ◽

Sabine Defasque ◽

Christine Fourcade ◽

JeanPierre Hurst ◽

Bertrand Joly

Keyword(s):

Multiple Myeloma ◽

Plasma Cells ◽

Chromosomal Abnormalities ◽

Conflicts Of Interest ◽

Critical Role ◽

Chromosome 8 ◽

Trisomy 8 ◽

Hematopoietic Stem ◽

Monosomy 7 ◽

Trisomy 12

Abstract Abstract 5063 Introduction, We describe the simultaneous presentation of multiple myeloma (MM) and yeloproliferative disorders (MPD) or lymphoid diseases (LD) at diagnosis. Therapy-related myelodysplasia (tMDS) occurring during the course of MM is generally believed as a result from hematopoietic stem cell-toxic therapies, such as ionizing radiation and alkylating agent-based chemotherapies (melphalan, nitrosoureas).Patients and methods, We study a total of 342 patients (151 F, 191 M; median age 68.1 years; range 42 to 93 Years), diagnosed with MM based on the International Staging System. The basis for inclusion of patients in this study was with previous untreated MM ones. The study was performed in accordance with the declaration of Helsinki. To determine whether chemotherapies for MM factors play the critical role in the development of secondary disease, simultaneously two different cultures were processed, an unstimulated 96 hours culture (U96HC) on whole BM(WBM), a short-time 24 hours culture (ST24HC) after CD138+ plasma cells (PCs) depleted on negative fraction (CD138- cells) of BM and the FISH was investigated on purified CD138+.All samples were enriched in PCs by the Automated Magnetic Cell Sorter (Miltenyi technology)proceeded with anti-CD138 specific antibodies applied. The CD138+ PCs and the CD138- cells were collected in different tubes. The CD138− cells were used for a ST24HC. FISH was performed on the purified CD138+, PCs with a recommended FISH panel (MM International Working Group). Screening was performed systematically for the following unbalanced alterations and reciprocal rearrangements: del(13)(q14)(D13S25), del(17)(p13)(TP53),+3(D3Z), +9(D9Z1), +15(D15Z14), t(4;14)(p16;q32)/IGH-FGFR3, t(11;14)(q13;q32)/IGH-CCND1 (Abbott).After observing the results of U96HC on whole BM (CD138+ and CD138− cells), ST24HC (CD138− cells) and FISH for each patient, two clone cytogenetically were distinct and unrelated chromosomal abnormalities were found in 40 (11.7%) of the 342 MM patients (6 F, 34 M; median age 74 years; range 42 to 87 Years) 34 had a MPD and 6 had a LD. A second immunophenotyping analysis confirmed the presence of those LD/MM simultaneous haematological malignancy. In the cases of the patients with MM/ MPD, the frequency of cytogenetic abnormality unrelated to the myeloma clone was respectively; the 20q deletion, detected for 13 the 34 patients, the 20q- is a sole abnormality for 12 cases and associated with a complex caryotype in 1 case. The trisomy of chromosome +8 was observed in 7 cases, the del(7q) or monosomy 7 in 5 cases, loss of gonosome Y in 4 cases, del(11) for 2 cases, translocation t(9;22) in one case, 5q abnormality in one case and trisomy 9 with JAK2 V617F mutation in one case. For the patients with MM/LD, 5 patients had a trisomy +12 and or trisomy +18 like sole abnormality or associated with others cytogenetics abnormalities and one patient had 6q deletion. Discussion, Whereas in the literature the most common cytogenetic abnormalities typifying MPD after alkylator-based therapy include partial or complete deletions of chromosomes 5, 7, and 20 as well as trisomy 8. In our study we observed those abnormalities with the same frequency for the patients had simultaneous MPD associated in untreated MM at diagnosis. Six patients had simultaneous LD and MM. The marginal zone lymphoma was confirmed for 3 patients. The CC observed a trisomy +12 for those three patients associated with +18 and +19 for 2 cases and del(13) and trisomy 3 for one among them. We demonstrated in untreated MM patients the coexistence of MM and MPD or LD at diagnosis with MPD-type or LD-type chromosome abnormalities within MM signature karyotype. We hence recommend that CC studies, 96 hours WBM, 24 hours on negative fraction CD138− cells and FISH on purified CD138+ PCs, the three should be an integral part of the evaluation of patients with MM at diagnosis into clinical trials using HDT is warranted to determine whether patients who are predisposed to developing tMDS/sAML, they can be identified prospectively. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

A Retrospective Evaluation of Clonal Cytogenetic Abnormalities in Ph Negative Clones in Patients with CP-CML on Therapy

Blood ◽

10.1182/blood.v112.11.4277.4277 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4277-4277

Author(s):

Monique A Hartley ◽

Bijal D. Shah ◽

Sady Armada ◽

Sara Tinsley ◽

Javier Pinilla

Keyword(s):

Kinase Inhibitors ◽

Chromosomal Abnormalities ◽

Treated Patient ◽

Philadelphia Chromosome ◽

Median Number ◽

Disease Course ◽

Trisomy 8 ◽

Monosomy 7 ◽

To Receive ◽

In Cells

Abstract Cytogenetic clonal aberrations in CML are a well recognized indicator of transition to blast phase. However, it is unclear how to interpret such changes when they occur in cells not harboring a Philadelphia Chromosome (Ph-), considering that some of these changes are often seen in patients with MDS/AML. In this retrospective review of 208 cases, we sought to determine the frequency, onset, character, and general course among CML patients harboring clonal chromosomal abnormalities (ChA) in Ph- cells during treatment with tyrosine kinase inhibitors (TKI’s). In this cohort, we were able to identify 13 ChA among 11 patients (5% of initial cohort), with most cases demonstrating trisomy 8 (31%), monosomy 7 (23%), and loss/gain of chromosome Y (38%). The median number of treatments per patient was 2 (1–3), with a median followup of 77.5 months (18–196 mo) among these 11 patients. Of the 13 ChA, 9 occurred during Imatinib therapy, and 5 of these 9 resolved without a change in medication. Of the remaining 4 patients, 2 presented with ChA prior to therapy, and 2 developed ChA while on a second generation TKI (Nilotinib, Dasatinib). The ChA persisted in the patient taking Nilotinib and resolved in the Dasatinib treated patient without change in therapy. Among those with ChA prior to therapy, the ChA resolved in one after the addition of INNO-406 (a lyn-abl inhibitor), and in the other despite going untreated between interval marrow specimens (this patient later went on to receive Imatinib with no ChA over an 18 month followup). CML disease course in patients with ChA in Ph- clones does not appear to be more severe, with only one patient having gone on to receive bone marrow transplantation for accelerated phase disease, and one other not currently in cytogenetic remission. Ten patients have attained complete (6) and major (4) molecular responses. Seven patients demonstrated cytopenias at last followup. Accompanying marrow dysplasia was seen among 4 of these patients. Interestingly, cytopenias are most pronounced in those with persistence of the ChA, including one patient with 5q deletion and another with chromosome 7 deletion. In summary, while clonal cytogenetic changes in Philadelphia Chromosome positive cells are a well recognized marker of disease progression, their presence in cells lacking this translocation does not seem to reflect a similar disposition. However while cytopenias of varying severity are noted in the patients reported, there is no evidence of transformation to MDS/AML nor a more resistant disease course. Long term follow up still is needed to confirm these data.

Download Full-text

Comparison of Clinical Outcomes Between Pediatric Aplastic Anemia and Refractory Cytopenia of Childhood

Blood ◽

10.1182/blood.v128.22.1498.1498 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1498-1498

Author(s):

Asahito Hama ◽

Atsushi Manabe ◽

Daisuke Hasegawa ◽

Kazue Nozawa ◽

Atsushi Narita ◽

...

Keyword(s):

Bone Marrow ◽

Aplastic Anemia ◽

Clinical Outcomes ◽

Who Classification ◽

Chromosomal Abnormalities ◽

Response Rates ◽

World Health ◽

Trisomy 8 ◽

Monosomy 7 ◽

Cell Lineages

Abstract In the diagnosis of childhood bone marrow failures (BMFs), differentiating aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (MDS) is challenging. The 2008 World Health Organization (WHO) classification has proposed a provisional entity, "refractory cytopenia of childhood (RCC)". The spectrum of patients with RCC is wide, ranging from patients with severe hypocellular bone marrow (BM) and mild dysplasia to those with normocellular BM and distinct dysplasia meeting the criteria for refractory cytopenia with multilineage dysplasia (RCMD) defined for adults with MDS. Currently, it is recommended that children who meet the criteria for RCMD should be classified as RCC in the WHO classification until the number of lineages involved has been fully evaluated with regard to their relative importance as prognostic factors. Until now, few studies have addressed the question whether the current WHO classification reflects clinical outcomes of childhood BMFs. To determine the clinical differences among AA, RCC, and RCMD, we compared clinical outcomes for patients with AA, RCC, and RCMD in Japan. From February 2009 to December 2013, 252 patients were registered to the central morphology review system of the Japanese Society of Hematology and Oncology and were diagnosed with BMFs. Peripheral blood (PB) and BM smears were reviewed by two pediatric hematologists, and BM trephine biopsies were reviewed by a hematopathologist. RCC is defined as persistent cytopenia with <2% and <5% blasts in PB and BM, respectively. BM aspirate smears show dysplastic changes in >2 cell lineages or >10% within one cell lineage. On the other hand, the criteria of RCMD is defined as persistent cytopenia with <1% and <5% blasts in PB and BM, respectively. BM smears show >10% dysplastic changes in >2 cell lineages. Patients with inherited BMFs were excluded by family history and physical examination. Further, Fanconi anemia was excluded by chromosome fragility test　and Dyskeratosis congenita was screened by measuring the telomere length of the peripheral lymphocytes by flowcytometry. Out of 252 patients, 63 were classified as AA, 131 as RCC, and 58 as RCMD. Median ages in AA, RCC, and RCMD groups were 10, 8, and 7 years, respectively (p=0.07). The median of leukocyte, neutrophil, reticulocyte, and platelet count, and mean corpuscular volume were significantly lower in AA than in RCC and RCMD groups (p<0.01). Chromosomal abnormalities were detected in 1 patient with AA (trisomy 8), 3 patients with RCC (trisomy 8, n=2; other, n=1), and 9 patients with RCMD (trisomy 8, n=5; monosomy 7, n=1; other, n=3) at the time of diagnosis (p<0.01). Out of 252 patients, 82 (AA, n=3; RCC, n=46; RCMD, n=33) were observed without any treatments (watch and wait, WW). 5-year overall survival (OS)/failure free survival (FFS) rates in WW group were 67%/67% in AA, 98%/54% in RCC, and 100%/69% in RCMD patients (p<0.01/p=0.97). Immunosuppressive therapy (IST) with rabbit antithymocyte globulin and cyclosporine was performed in 110 (AA, n=39; RCC, n=57; RCMD, n=14) patients. Six months after the IST, the response rates to the IST were not significantly different among AA (40%), RCC (63%), and RCMD (64%) (p=0.08). The development of additional chromosomal aberrations was found in 2 patients with RCC, and 1 with RCMD. The 5-year OS/FFS rates in IST group were 89%/36% in AA, 94%/38% in RCC, and 93%/23% in RCMD patients (p=0.64/p=0.86). Stem cell transplantation (SCT) as a first line therapy was performed in 19 patients with AA, 10 with RCC, and 5 with RCMD. The rejection was found in 2 patients with RCC and 3 with RCMD. Although 5-year OS rates in patients who underwent SCT were not different among 3 groups (p=0.26), FFS rate (30%) in patients with RCMD was significantly lower than in those with AA (100%) and RCC (78%) (p<0.01). In conclusion, we could not find any clinical relevance of separating RCC from AA because response rates to IST and the development of clonal evolution did not significantly differ between AA and RCC. The entity of RCMD should be adopted to childhood MDS classification because children with RCMD exhibited a distinct characteristic of morphology and a frequent chromosomal aberration at the time of diagnosis. The optimal treatment strategy including preconditioning regimen of SCT should be established for children with acquired BMFs based on the BM cellularity and morphological classification. Disclosures Kojima: SANOFI: Honoraria, Research Funding.

Download Full-text

Fas-mediated apoptosis is important in regulating cell replication and death in trisomy 8 hematopoietic cells but not in cells with other cytogenetic abnormalities

Blood ◽

10.1182/blood-2002-01-0096 ◽

2002 ◽

Vol 100 (13) ◽

pp. 4427-4432 ◽

Cited By ~ 58

Author(s):

Elaine M. Sloand ◽

Sonnie Kim ◽

Monika Fuhrer ◽

Antonio M. Risitano ◽

Ryotaro Nakamura ◽

...

Keyword(s):

Bone Marrow ◽

Fas Ligand ◽

Chromosomal Abnormalities ◽

Bone Marrow Cells ◽

Active Role ◽

Trisomy 8 ◽

Normal Cells ◽

Monosomy 7 ◽

Fresh Bone ◽

Fas L

Increased apoptosis of hematopoietic progenitor cells has been implicated in the pathophysiology of cytopenias associated with myelodysplastic syndromes (MDSs), and inhibition by immunosuppression may account for the success of this treatment in some patients. We examined bone marrow and peripheral blood of 25 patients with chromosomal abnormalities associated with MDS (monosomy 7, trisomy 8, and 5q−) for evidence of apoptosis. When fresh bone marrow was examined, the number of apoptotic and Fas-expressing CD34 cells was increased in patients with trisomy 8, but decreased in monosomy 7, as compared with healthy control donor marrow. Fas expression was increased in the trisomy 8 cells and decreased in the monosomy 7 cells when compared with normal cells from the same patient. Trisomy 8 cells were more likely to express activated caspase-3 than were normal cells. For bone marrow cells cultured with Fas agonist or Fas antagonist, the percentage of cells with trisomy 8 was significantly decreased in most cases after Fas receptor triggering and increased by Fas ligand (Fas-L) antagonist (P < 0.01), suggesting increased Fas susceptibility of cells with trisomy 8. No such changes were seen in cultures of cells with 5q− or monosomy 7. Fas antagonist facilitated the expansion of cells with trisomy 8 only. Cells with trisomy 8 appear to be more susceptible to Fas-mediated apoptosis. Clinical data demonstrating the responsiveness of some patients with trisomy 8 to anti–thymocyte globulin (ATG) and cyclosporine (CsA) would favor an active role of the immune system in this syndrome.

Download Full-text

Incidence and Clinical Significance of Scoring System in Myelodysplastic Syndromes Including Hematological and Cytogenetic Profiles from a Single Institution

Blood ◽

10.1182/blood.v112.11.5102.5102 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5102-5102

Author(s):

Myungshin Kim ◽

Jihyang Lim ◽

Yonggoo Kim ◽

Kyungja Han ◽

Yoo-Jin Kim ◽

...

Keyword(s):

Scoring System ◽

Who Classification ◽

Chromosomal Abnormalities ◽

Chromosome Analysis ◽

World Health ◽

International Prognostic Scoring System ◽

Good Prediction ◽

Trisomy 8 ◽

Long Time ◽

Health Organization

Abstract Background: Mydelodysplastic syndromes (MDS) are clonal stem cell disorders characterized by hypercellular marrow with ineffective hematopoiesis determining peripheral cytopenia. Recently, the WHO developed a new classification that identifies the following subtypes: RA, RARS, 5q- syndrome (MDS 5q-), RCMD, RCMD with ringed sideroblasts (RCMDS), RAEB-1, RAEB-2 and MDS unclassifiable (MDS-U). The goals of our study were to establish the incidence of chromosome abnormalities in MDS patients, to correlate chromosomal defects with WHO subtype and peculiar clinical-biological findings. Patients and Methods: We studied 242 consecutive MDS patients who were admitted in the hematology department of St. Mary’s hospital from 2000 to 2007. The diagnosis was made according to the World Health Organization classification system. The chromosome analysis of the BM cells at diagnosis was performed by the G-staining method with trypsin and karyotyped according to the ISCN 2005. Results: The median age of patients was 50 (2–84). WHO classification was as follows: RA (n=21, 8.7%), RARS (n=7, 2.9%), RCMD (n=62, 25.6%), RCMDS (n=6, 2.5%), RAEB-1 (n=63, 26.0%), RAEB-2 (n=74, 30.6%), MDSU (n=7, 2.9%), MDS 5q- (n=2, 0.8%). Chromosomal abnormalities were found in 51.2% of patients. The cases with good, intermediate and poor cytogenetic risk features were observed in 55.0%, 29.3%, and 15.7%. Trisomy 8 was most common abnormality in all cases. 1q+, 5q-, 20q- were followed. By International Prognostic Scoring System (IPSS) 13 (5.4%) patients were classified in low group; 141 (58.3%) intermediate-1, 60 (24.8%) intermediate-2, and 28 (11.6%) high were classified. By WHO classification-based prognostic scoring system (WPSS), 14 (5.8%) patients were classified in very low group; 25 (10.3%) low, 57 (23.6%) intermediate, 110 (45.5%) high, and 36 (14.9%) very high were classified. Thirty-six patients (14.9%) progressed into AML. Both IPSS and WPSS was shown to predict survival and leukemia progression, even in a short-term prospective study (P<0.001). Conclusions: It is important to diagnose MDS accurately on the base of cytopenia, bone marrow morphology and clonal chromosomal abnormalities. IPSS and WPSS provide good prediction of survival and risk of leukemic evolution in MDS patients. The evaluation of clinical, hematological and cytogenetic analysis in more cases for long time follow-up will be helpful to standardize diagnosis of MDS.

Download Full-text

Cytogenetic Profile of Lymphoma of Follicle Mantle Lineage: Correlation With Clinicobiologic Features

Blood ◽

10.1182/blood.v93.4.1372 ◽

1999 ◽

Vol 93 (4) ◽

pp. 1372-1380 ◽

Cited By ~ 65

Author(s):

Antonio Cuneo ◽

Renato Bigoni ◽

Gian Matteo Rigolin ◽

Maria Grazia Roberti ◽

Antonella Bardi ◽

...

Keyword(s):

Statistical Significance ◽

Bone Marrow Involvement ◽

Normal Karyotype ◽

Chromosome Analysis ◽

Prognostic Indicator ◽

Lymph Node Involvement ◽

Fish Analysis ◽

Strong Impact ◽

Trisomy 12 ◽

Cytogenetic Profile

Abstract Conventional chromosome analysis (CCA) and interphase fluorescence in situ hybridization (FISH) was performed in 42 patients with mantle-cell lymphoma (MCL), with BCL1 rearrangement. The t(11;14)(q13;q32) or 11q abnormalities were detected by CCA in 34 cases, 20 of which had additional aberrations. A normal karyotype was observed in 8 cases. Probes detecting the chromosome aberrations that were observed in at least 3 cases by CCA, ie, +12, 13q14 deletion, and 17p deletion, were used for interphase FISH analysis. FISH detected total or partial +12, 13q14 deletion and 17p- in 28.5%, 52.4%, and 26% of the cases, respectively. The presence of these anomalies was not a function of karyotype complexity. Based on the results of CCA/FISH, three groups of increasing karyotype complexity were recognized: group 1, including 11 patients without detectable aberrations in addition to BCL1 rearrangement; group 2, including 14 patients with 1 to 2 additional anomalies; and group 3, including 17 patients with three or more additional anomalies. Clinical parameters associated with shorter survival were male sex (P= .006) and primary lymph-node involvement compared with primary bone marrow involvement (P = .015). Trisomy 12 was the only single cytogenetic parameter predictive of a poor prognosis (P = .006) and the best prognostic indicator was the derived measure of karyotype complexity (P < .0001), which maintained statistical significance in multivariate analysis (P< .0001). We arrived at the following conclusions: 13q14 deletion occurs at a high incidence in MCL; 17p deletion and total/partial +12 are relatively frequent events in MCL, the latter aberration being associated with a shorter survival; and the degree of karyotype complexity has a strong impact on prognosis in this neoplasia.

Download Full-text

Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia

Blood ◽

10.1182/blood.v99.9.3129 ◽

2002 ◽

Vol 99 (9) ◽

pp. 3129-3135 ◽

Cited By ~ 164

Author(s):

Jaroslaw P. Maciejewski ◽

Antonio Risitano ◽

Elaine M. Sloand ◽

Olga Nunez ◽

Neal S. Young

Keyword(s):

Aplastic Anemia ◽

Chromosomal Abnormalities ◽

Bone Marrow Cells ◽

Chromosome 7 ◽

Trisomy 8 ◽

Monosomy 7 ◽

Cytogenetic Abnormalities ◽

Constant Rate ◽

Structural Abnormalities ◽

Actuarial Risk

Abstract A serious complication of aplastic anemia (AA) is its evolution to clonal hematologic diseases such as myelodysplasia (MDS) and leukemia, which is usually associated with the appearance of a cytogenetic abnormality in bone marrow cells. We present here an analysis of a cohort of 30 patients with otherwise typical AA in whom clonal karyotypic evolution was observed during frequent periodic marrow examinations. The actuarial risk for this complication has been estimated in other studies at around 15% at 5 years. Conversion from normal to abnormal karyotype occurred at a constant rate after initial diagnosis, with about 50% of cases developing within the first 30 months. Transient chromosomal abnormalities were infrequent. Clinically, AA patients with clonal cytogenetic patterns were heterogenous; a variety of karyotypic defects with numerical and structural abnormalities of chromosome 7 accounted for 40% of all cases followed by trisomy 8, structural and numerical abnormalities of chromosome 13, deletion of Y chromosome, and complex cytogenetic abnormalities. Unlike in primary MDS, aberrancies of chromosome 5 and 20 were infrequent. The clinical course depended on the specific abnormal cytogenetic pattern. Most deaths related to leukemic transformation occurred in patients with abnormalities of chromosome 7 or complex cytogenetic alterations or both. Evolution of chromosome 7 abnormalities was seen most often in refractory patients who had failed to respond to therapy. In contrast, trisomy 8 developed in patients with good hematologic responses who often required chronic immunosuppression with cyclosporine A (CsA), and survival was excellent. Although AA patients with monosomy 7 showed a similar prognosis to those with primary MDS, trisomy 8 in AA appears to have a more favorable prognosis than in MDS.

Download Full-text

Detection of monosomy 7 and trisomy 8 in myeloid neoplasia: a comparison of banding and fluorescence in situ hybridization

Blood ◽

10.1182/blood.v82.3.904.904 ◽

1993 ◽

Vol 82 (3) ◽

pp. 904-913 ◽

Cited By ~ 64

Author(s):

RE Kibbelaar ◽

JW Mulder ◽

EJ Dreef ◽

H van Kamp ◽

WE Fibbe ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Therapy Monitoring ◽

Fish Analysis ◽

Trisomy 8 ◽

Interphase Cytogenetics ◽

Monosomy 7 ◽

Alphoid Dna ◽

Myeloid Neoplasia

Abstract Fluorescence in situ hybridization (FISH) is a powerful tool for detection of numerical and structural chromosomal aberrations. We have compared conventional banding techniques and FISH for the detection of monosomy 7 (-7) and trisomy 8 (+8) in 89 patients with myeloid malignancies. Of these patients, 21 had -7, 30 had +8, four had both, and 34 had no aberrations or aberrations other than -7 or +8 as assessed by banding techniques. Sequential samples were available in 23 patients. Alphoid DNA probes specific for chromosomes no. 7 and 8 were used for FISH. As controls, 10 normal bone marrow (BM) samples were hybridized with the chromosomes no. 7 and 8 probes, and in addition all tumor samples were hybridized with a chromosome no. 1 specific probe. The cut-off value for -7 was 18% one-spot cells, and for +8 was 3% three-spot cells. FISH analysis of 44 samples with -7 or +8, and at least 10 metaphases evaluated, showed that the proportions of aberrant metaphase cells mirrored the interphase clone sizes. Most samples with nonclonal metaphase aberrations, including those with only a few metaphases, had increased numbers of aberrant interphase cells: 20% to 80% for -7, and 3% to 43% for +8. Interphase cytogenetics of the 34 samples without -7 or +8 did not show significant cell populations with -7 or +8. In four patients, -7 or +8 could not be confirmed by FISH due to additional structural aberrations, marker chromosomes, or wrongly interpreted banding results. As FISH will be used more and more in cytogenetic diagnosis, clinical follow-up, and therapy monitoring, it will be necessary to standardize FISH procedures and supplement the Standing Committee on Human Cytogenetic Nomenclature (ISCN) definitions of a clone with criteria specifically for in situ hybridization.

Download Full-text