Study On the Clonal Origin of Dysplastic Cells by Fluorescence in Situ Hybridization in Myelodysplastic Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4858-4858
Author(s):  
Jun Zhang ◽  
Yongquan Xue ◽  
Jinlan Pan ◽  
Yafang Wu ◽  
Juan Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Myelodysplastic Syndromes ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Banding Technique ◽  
Clonal Origin

Abstract Abstract 4858 Objective To determining the clonal origin of dysplatic cells in Myelodysplastic syndromes (MDS) . Methods Karyotypic analyses of bone marrow cells using R-banding technique were carried out to determine the chromosomal abnormalities. Interphase fluorescence in situ hybridization (FISH) and morphologic analysis of bone marrow aspirates were performed in the same cells to investigate the clonal origin of dysplatic cells in 8 MDS patients. Result All patients had clonal karyotypic abnormalities: simple abnormality in 1 patient, complex abnormalities in 6 patients, coexistent of two unrelated clones in 1 patient. Most of dysplastic cells in 7 of 8 MDS patients derived from neoplasia clone while 1 patient had a reverse result,no matter what cell lineage was involved. Some of non-dysplastic cells of all patients derived from malignant clone; in 7 patients, the proportion of dysplastic cells in malignant clone were significantly higher than that of non- malignant clone. Conclusion Most of dysplastic cells in MDS derived from malignant clones, while the minority of them derived from non-malignant clones. Thus, it is reasonable to expect that in most cases myelodysplasia is present in malignant clone and can be taken as an important diagnostic evidence for MDS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Detection of residual leukemic cells in patients with acute promyelocytic leukemia by the fluorescence in situ hybridization method: potential for predicting relapse

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 495-499 ◽  
Author(s):  
L Zhao ◽  
KS Chang ◽  
EH Estey ◽  
K Hayes ◽  
AB Deisseroth ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Acute Promyelocytic Leukemia ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Low Frequencies

Abstract The translocation between chromosomes 15 and 17, t(15;17)(q22–24;q11– 21), is present in the bone marrow cells of most patients with acute promyelocytic leukemia (APL). Although conventional cytogenetic methods are useful for diagnosing this disease, difficulties are experienced in detecting residual disease among those patients who have achieved remission. In this study, we used the fluorescence in situ hybridization (FISH) method to attempt to detect residual leukemic cells in 10 APL patients in clinical remission. The duration of remission ranged from 2 to 93 months at the time of study. Multiple bone marrow samples were analyzed by FISH in most patients. In 6 patients, no cell with t(15;17) was found. These patients remain in complete remission at present (approximately 25 to 33 months since first studied by FISH). In 4 patients, low frequencies of cells with t(15;17) were observed in at least one bone marrow sample examined. All of these patients relapsed within 1 to 14 months. No cell with t(15;17) was identified by the conventional G-banding method in any sample. The FISH results correlated well with that of a two-round nested reverse transcription polymerase chain reaction assay that was performed on the same samples. Thus, our study suggests that FISH is potentially a useful tool for detecting residual APL cells and for identifying patients at high risk of relapse.

Association of Interphase Fluorescence in Situ Hybridization (IP-FISH) Response Criteria with Conventional Metaphase Cytogenetics in CML Patients On Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4707-4707
Author(s):  
Thomas Schenk ◽  
Martin C Müller ◽  
Alice Fabarius ◽  
Philipp Erben ◽  
Thomas Ernst ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Conflicts Of Interest ◽  
False Negative ◽  
Response Criteria ◽  
Interphase Cells ◽  
Definition Of ◽  
Fish Response

Abstract Abstract 4707 The Philadelphia (Ph) chromosome and its molecular equivalent, the BCR-ABL fusion gene, represent the pathogenetic cause and a useful marker for diagnosis and follow up monitoring of chronic myeloid leukemia (CML). Cytogenetic analysis of bone marrow metaphases (Cy) has been established as the standard method. In contrast, interphase fluorescence in situ hybridization (IP-FISH) has been increasingly applied in many studies due to recent optimization of the technique but is not represented in current treatment guidelines. We therefore sought to define IP-FISH response criteria which correspond best with complete (CCyR) and major cytogenetic responses (MCyR). In order to quantitatively compare results of both methods 1,749 consecutive non selected bone marrow samples from 748 CML patients at different stages of CML were analyzed in parallel with Cy and IP-FISH. 5 patients with Ph negative/BCR-ABL positive CML were excluded from the analysis. 643 patients in chronic phase (CP) were analyzed during imatinib based therapy, ten patients received interferon alpha. 74 patients at different stages of the disease received 2nd generation tyrosine kinase inhibitors: nilotinib, n=18 (CP, n=13; accelerated phase, AP, n=2; blast crisis, BC, n=3); dasatinib, n=56 (CP, n=41; AP, n=4; BC, n=11). 21 patients received no therapy or the therapy was not evaluable. The correlation between Ph positive metaphases and the proportion of FISH positive interphase cells was determined using the Spearman's rank correlation coefficient. The chi-square test was used to compare IP-FISH and Cy data. The optimally separating threshold value between Cy and IP-FISH was chosen as cut-off point. Cy and IP-FISH data correlated well (r=0.89; p<0.0001). The following cut-off values were defined: '30% IP-FISH positivity was found to correspond best with MCyR ('35% Ph+ metaphases); <6% IP-FISH positivity was concordant with CCyR (0% Ph+ metaphases). Of 1,163 samples of patients in CCyR, 99.1% showed a percentage of <6% IP-FISH positive cells. 82 of 1,163 samples (7.0%) with 0% Ph+ metaphases by Cy were IP-FISH positive (median 3%, range, 1-21% positive interphases). IP-FISH showed false negative results in 10 of 1,090 samples (0.9%) with a median of 8% Ph+ metaphases (range, 4-40%). Using these IP-FISH cut-off points, the diagnostic specificity for the definition of CCyR was 93.8% for all patients and 93.7% for CP pts only and for the definition of MCyR 89.4% for all patients and 88.4% for CP patients only, respectively. In conclusion, BCR-ABL FISH data derived from bone marrow interphase cells are comparable with metaphase cytogenetics but the cut-off points differ. IP-FISH might be used instead of Cy in order to assess the achievement of response milestones in CML patients during therapy. The prognostic value of IP-FISH data, however, should be analyzed in prospective controlled trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Detection of residual leukemic cells in patients with acute promyelocytic leukemia by the fluorescence in situ hybridization method: potential for predicting relapse

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 495-499
Author(s):  
L Zhao ◽  
KS Chang ◽  
EH Estey ◽  
K Hayes ◽  
AB Deisseroth ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Acute Promyelocytic Leukemia ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Low Frequencies

The translocation between chromosomes 15 and 17, t(15;17)(q22–24;q11– 21), is present in the bone marrow cells of most patients with acute promyelocytic leukemia (APL). Although conventional cytogenetic methods are useful for diagnosing this disease, difficulties are experienced in detecting residual disease among those patients who have achieved remission. In this study, we used the fluorescence in situ hybridization (FISH) method to attempt to detect residual leukemic cells in 10 APL patients in clinical remission. The duration of remission ranged from 2 to 93 months at the time of study. Multiple bone marrow samples were analyzed by FISH in most patients. In 6 patients, no cell with t(15;17) was found. These patients remain in complete remission at present (approximately 25 to 33 months since first studied by FISH). In 4 patients, low frequencies of cells with t(15;17) were observed in at least one bone marrow sample examined. All of these patients relapsed within 1 to 14 months. No cell with t(15;17) was identified by the conventional G-banding method in any sample. The FISH results correlated well with that of a two-round nested reverse transcription polymerase chain reaction assay that was performed on the same samples. Thus, our study suggests that FISH is potentially a useful tool for detecting residual APL cells and for identifying patients at high risk of relapse.

Multiple Myeloma, Detection of Four Unfavorable Genetic Pronostic Factor by Interphase Two-Color Fluorescence in Situ Hybridization Analyses: A Study of 33 Patients At Diagnosis or Relapse

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5004-5004 ◽  
Author(s):  
Carlo Sergio Barragan ◽  
Silvia B. Hansson ◽  
Silvina A Cicchini ◽  
Federico J Hidalgo ◽  
Claudia E Ochoa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Poor Prognosis ◽  
Conflicts Of Interest ◽  
Autologous Bone Marrow Transplantation ◽  
Chromosome Band ◽  
Chemotherapy Drugs ◽  
Genomic Aberrations

Abstract Abstract 5004 Background: Interphase Fluorescence in situ hybridization (FISH) has improved the detection of early bad prognostic genomic aberrations in Myeloma (MM) is a fast and reliable method. We used this assay in myeloma patients at diagnosis, after relapse or treatment failure. Methods: Interphase Mononuclear cells from Bone Marrow of 36 Caucasian patients, 13 men and 23 women, age ranged from 40 to 84 years (median, 64) with MM. were analyzed by LEXEL Live FISH probes, for deletions in chromosome band 13q14. 3, 17p13. 1; IGH/CCND1 translocation dual fusion and cMYC breakapart 8 Chromosome. Results: Chromosomal aberrations were detected in 16 of 33 evaluable patient samples of a total 36 patients population. The most frequent aberrations were 7/16 in 13p14. 3 band deletion (43. 75%) 7/33 (21%); 5/16 (31, 25%)patients with deletion had 17p13. 15/33 (15, 15%); 3 cMYC breakapart 3/16 (18. 75%) 3/33 (9%); IGH/CCND1 translocation in 3 patients 3/16 (18. 75%) 3/33 (9%), two of them associated one with cMYC and the other with 13p14. 3. We found other association: A)13p14. 3; 17p13. 1 and cMYC in (1/33). B) 13p14. 3 and cMYC (1/33) C) 17p13. 1; cMYC (1/33). Two patients had 8 chromosome trisomy 2/33 (6%). We foun that 13p14. 3, 17p13. 1 and cMYC association was correlated with a worst and fast evolution. Who had 13p14. 3 band deletion had a worst evolution in our patients. cMyc was associated with a poor prognosis. Conclusions: Genomic aberrations are independent prognosis factors of disease progression, chemotherapy respond and survival in Myeloma. Novel DNA molecular target and bone marrow micro environment modification drugs such as bortezomib and thalidomide or lenalidomide must be use in first line associated perhaps with standar chemotherapy drugs for improving result and consolidate this patients with autologous bone marrow transplantation avoiding the dilate of this strategic in patient with poor prognosis. Future trials must be performed to include a more complete panel of probes in Myeloma. Disclosures: No relevant conflicts of interest to declare.

Whole Chromosome Painting and Multiplex Fluorescence In Situ Hybridization in Detecting Complex Chromosomal Aberrations in Myelodysplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4853-4853
Author(s):  
Jianyong Li ◽  
Bing Xiao ◽  
Lijuan Chen ◽  
Yu Zhu ◽  
Wei Xu ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Chromosomal Aberrations ◽  
Myelodysplastic Syndromes ◽  
Chromosome Painting ◽  
Banding Technique ◽  
Marker Chromosomes ◽  
Molecular Cytogenetic ◽  
Whole Chromosome Painting

Abstract Objective To explore the value of the technique of whole chromosome painting (WCP) and multiplex fluorescence in situ hybridization (M-FISH) in the detection of complex chromosomal aberrations (CCAs) of myelodysplastic syndromes (MDS). Methods M-FISH was used in seven MDS patients with CCAs detected by R-banding technique to refine CCAs, and to identify cryptic translocations and characterization of marker chromosomes. Dual-color WCP procedures were further performed in 7 cases to confirm some rearrangements detected by M-FISH. Results In all cases, M-FISH confirmed all results of R-banding.The composition and origin of 6 kinds of marker chromosomes, 9 kinds of chromosomes with additional material undetermined and 5 kinds of derivative chromosomes undefined by CC were defined after M-FISH analysis; 4 kinds of cryptic translocations overlooked by CC were found on derivative chromosomes and previously normal appearing chromosomes. In addition, M-FISH revealed some nonrandom aberrations: aberrations involving chromosome 17 (5/7) and -5/5q- (4/7) were the two most frequent aberrations. Fluorescence flaring is a main factor leading to misinterpretations. Some misclassified and missed chromosomal aberrations by M-FISH were corrected by WCP. Conclusions M-FISH is a powerful molecular cytogenetic tool in clarification of CCAs. Complementary WCP helped us identify misclassified and missed chromosomal aberrations by M-FISH. CC in combination with molecular cytogenetic techniques M-FISH and WCP can unravel complex chromosomal aberrations more precisely.

Probing the pathobiology of response to all-trans retinoic acid in acute promyelocytic leukemia: premature chromosome condensation/fluorescence in situ hybridization analysis

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 218-226 ◽  
Author(s):  
RC Vyas ◽  
SR Frankel ◽  
P Agbor ◽  
WH Jr Miller ◽  
RP Jr Warrell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
In Situ Hybridization ◽  
Complete Remission ◽  
Fluorescence In Situ Hybridization ◽  
Bone Marrow Cells ◽  
Promyelocytic Leukemia ◽  
Premature Chromosome Condensation ◽  
Trans Retinoic Acid

Abstract The response of acute promyelocytic leukemia (APL) peripheral blood and bone marrow cells to trans-retinoic acid (RA) was cytogenetically characterized during RA treatment using the techniques of premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH). Before treatment, the predominant immature bone marrow cells were found to have t(15;17), whereas the residual mature granulocytes were diploid and lacked evidence of the translocation. In response to RA treatment, an increase in the leukocyte count was noted. The majority of these cells exhibited a t(15;17). Subsequently (eg, between days 6 and 23), 32% to 91% of the maturing myeloid cells still exhibited t(15;17). The appearance of t(15;17) in gradually maturing elements suggests that RA contributed to a release of the maturation block of the leukemic elements. As responding patients obtained complete remission, diploid elements without evidence of the translocation prevailed in the blood and bone marrow. In 16 patients studied after 1 month in complete remission, all but 2 showed all diploid cells. The residual t(15;17) cells disappeared 18 days later in 1 patient, whereas the second patient exhibited clinical evidence of relapse 20 days later. These results suggest that response of patients with APL to RA is associated with maturation, subsequent loss of the mature leukemic elements, and preferential regeneration of normal diploid hematopoietic elements.

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