scholarly journals Retrospective evaluation of chromosome 1 anomalies in hematologic malignancies: A single center study

2019 ◽  
Vol 3 (3) ◽  
pp. 17
Author(s):  
Süreyya Bozkurt ◽  
Müfide Okay ◽  
Filiz Sağlam ◽  
İbrahim C Haznedaroğlu
Keyword(s):  
Bone Marrow ◽  
Cytogenetic Analysis ◽  
Hematologic Malignancies ◽  
Chromosome 1 ◽  
Chromosomal Anomalies ◽  
Image Analysis System ◽  
Conventional Cytogenetic Analysis ◽  
Single Center Study ◽  
Genetic Aberration ◽  
Analysis System

Various anomalies of chromosome 1 which is the biggest chromosome among all human chromosomes were found in various hematologic diseases. In this retrospective study, clinical features and cytogenetic anomalies of 35 hematological patients with various chromosome 1 anomalies were correlated. Also the effect of chromosome 1 anomalies to the prognosis of those patients was discussed. Conventional cytogenetic analysis of those patients was performed by investigating metaphases of 24 hours stimulated bone marrow samples. After cell culturing, the samples were treated with tripsin and stained with Giemsa (GTG Banding). Analyses were performed on image analysis system (Metasystem, Germany). Chromosome 1 anomalies were determined in 35 patients (0.5 %) among 6865 samples having done their conventional bone marrow cytogenetic analysis in our center between January 2008 and March 2016. The ratio of chromosome 1 anomalies of totally 701 anomalies among 6865 patients was 4.9 %. Chromosome 1 anomalies were found mostly in patients with MM, MDS and AML in our study group. The most common anomaly was deletion 1 which was seen in 16 (37%) of the patients. Second most common anomaly was derivation 1 which was seen in 13 (30%) of the patients. Also translocations of chromosome 1 with other chromosomes were seen. The genetic aberration formed as a result of chromosomal anomalies result in the formation of hematologic malignancies. The effect on disease pathogenesis and prognosis of some of those anomalies is known and some needs to be investigated and determined.

Classical and Molecular Cytogenetic Abnormalities in 124 Pediatric Patients with Acute Lymphocyte Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4419-4419
Author(s):  
Yihuan Chai ◽  
Hui Lv ◽  
Jun Lu ◽  
Peifang Xiao ◽  
Jianqing Li
Keyword(s):  
Bone Marrow ◽  
Multiplex Pcr ◽  
Cytogenetic Analysis ◽  
Chromosomal Abnormalities ◽  
Molecular Diagnostic ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Childhood All ◽  
Cytogenetic Abnormalities ◽  
Conventional Cytogenetic Analysis

Abstract In childhood acute lymphocyte leukemia (ALL), cytogenetics plays an important role in diagnosis, allocation of treatment and prognosis. On base of the conventional cytogenetic analysis, molecular methods have inproved our ability to accurately and rapidly risk-stratify patient with childhood ALL in the last few years. Our aim was to assess the demography of cytogenetic abnormalities in childhood ALL. The study sample consisted of 124 newly diagnosed ALL patients younger than 16 years, who were diagnosed at the Department of Pediatric Hematology/Oncology, Soochow University Children’s Hospital. The diagnosis and FAB subtypes of ALL was determined by Wright-Giemsa-stained bone marrow smears and cytochemicalstaining. Immunophenotyping of the bone marrow samples was performed by flow cytometry. Multiplex reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed to detect the 29 most common leukemia translocations for routine molecular diagnostic hematopathology practice, and complement the information gained from conventional cytogenetic analysis. Cytogenetic analysis was successful in 112 of 124 children with ALL. Sixty-eight (60%)of them had clonal chromosomal abnormalities. Numerical imbalances consisted of hyperdipoild(>47 chromosomes, 36 cases), hypodipoild(<46 chromosomes, 14 cases), pseudodiploidy(18 cases). Chromosomal translocations were observed in 13 patients by conventional cytogenetic analysis. Three cases were found positive for t (4;11), 3 cases for t (9;22), 1 case for t (1;19) and 6 cases for other rare translocations. RT-PCR analysis detected 116 of the 124 ALL patients. Thirteen cases of TEL-AML1, 10 cases of rearrangement in the MLL gene, 4 cases of E2A-PBX1, 4 cases of E2A-HLF, 3 cases of BCR-ABL, 2 cases of TLS-ERG, 32 cases of HOX11, were detected by RT-PCR in B-lineage leukemias. SIL-TAL1 had been found in 4 of 7 of T-lineage leukemias. Sixty-eight cases of ALL show chromosomal aberrations. Multiplex PCR positivity was detected in 59(50%)of the 116 ALL patients studied. Multiplex PCR combined with chromosome analysis uncovered Chromosomal abnormalities in 95 of 124(77%) of ALL patients and supplemented each other in detecting Chromosomal abnormalities. It provides reliable evidence for the diagnosis, classification and prognosis.

Complex Karyotypic Abnormalities Detected by Conventional Cytogenetic Analysis More Strongly Predict Survival Than FISH, ZAP70, or IgVH Mutation Status for Previously Treated Patients with CLL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2065-2065
Author(s):  
William G. Wierda ◽  
S. O’Brien ◽  
S. Faderl ◽  
A. Ferrajoli ◽  
G. Garcia-Manero ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factors ◽  
High Risk ◽  
Cytogenetic Analysis ◽  
Independent Predictor ◽  
Alkylating Agents ◽  
Mutation Status ◽  
Conventional Cytogenetic Analysis ◽  
Previously Treated Patients ◽  
Previously Treated

Abstract Recently, several novel prognostic factors have been identified; their significance has been demonstrated in selected patient (pt) populations and retrospective analyses. As a group, previously treated pts with CLL likely have their respective, relevant prognostic factors for clinical endpoints, which may be further impacted by treatment (Rx). We prospectively evaluated the significance of newer prognostic factors: FISH abnormalities (abn) (Vysis CLL panel), IgVH mutation status, ZAP70 expression (flow & immunohistochemistry), CD38 expression (≥30%); as well as traditional factors: conventional cytogenetic analysis perfomed on bone marrow metaphases, age, sex, # prior Rx, refractoriness to alkylating agents (ALK) or fludarabine (FLU), absolute lymphocyte count (ALC), HGB, PLT, β-2 microglobulin (B2M), ALB, LDH, creatinine, and Alk Phos as independent predictors for survival in previously treated pts. The group included 473 previously treated pts seen at M.D.Anderson (10/03–8/07), who were evaluated by bone marrow sampling with conventional and FISH cytogenetic analyses, and the new and traditional prognostic factors described above. The median (range) age was 63yrs(31–87) and # prior Rx was 2(1–13). Other characteristics were: 43% Rai high-risk; 35% FLU-refractory; and 39% ALK-refractory; 74% unmutated IgVH; 54% ZAP70+ (flow); 76% ZAP70+ (IHC); and 68% CD38+. FISH results were: 22% del 17p13, 21% del 11q22, 10% +12, and 48% del 13q14 or no abn by the hierarchical classification. Conventional cytogenetic analysis of bone marrow metaphases demonstrated 25% with a complex karyotypic abn (&gt;1 cell with &gt;1 chromosome abn), 58% diploid, 17% with single clonal abn (&gt;1 cell with 1 abn). Of the 100 pts with complex karyotypic abn, 50% had del 17p13, 28% del 11q22, 6% +12, 9% del 13q14, and 7% had no abn by FISH. Survival was measured from the time of prognostic factor characterization (FISH). The median follow-up time was 10mo(0–47). Univariate analyses identified the following significant (p≤.01) predictors for shorter survival: advanced age, # prior Rx, Rai high-risk, ALK- or FLU-refractory, FISH del 17p13; complex karyotypic abn (Figure 1), unmutated IgVH, high ALC, low HGB, low PLT, high B2M, low ALB, high LDH, and high Alk Phos. Multivariate analysis produced the following model with the following significant (p&lt;.05) independent predictors for survival: ALK- (HR 2.2) or FLU-refractory (1.9), complex karyotypic abn (HR 1.8), PLT (HR 0.99), and ALB (HR 0.35). We previously reported complex karyotypic abn as a significant independent predictor for shorter survival in previously treated patients receiving chemoimmunotherapy (JCO23:4070, 2005). These data indicate that for previously treated pts with CLL, a complex karyotypic abn detected by conventional cytogenetic analysis is a strong independent predictor for survival and appears superior to FISH, and other newer prognostic factors such as IgVH mutation status and ZAP70 expression. Figure Figure

Cytogenetic Analysis in Patients with Newly Diagnosed Myelodysplastic Syndromes in Southern Italy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 50623-50623
Author(s):  
Esther Natalie Oliva ◽  
Francesco Albano ◽  
Nicola Di Renzo ◽  
Vincenzo Pavone ◽  
Stefano Molica ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Cytogenetic Analysis ◽  
Southern Italy ◽  
Conflicts Of Interest ◽  
Refractory Anemia ◽  
Newly Diagnosed ◽  
Conventional Cytogenetic Analysis ◽  
Conventional Analysis ◽  
Italian Regions

Abstract Abstract 50623 Background: Bone marrow karyotype in myelodysplastic syndromes (MDS) is essential to define the prognosis and to guide treatment decisions, including targeted therapies. Due to the lack of an extensive national MDS registry in Italy, epidemiological data on MDS, including cytogenetics, throughout the territory is unknown. Objective: We evaluated the incidence of cytogenetic abnormalities amongst newly diagnosed MDS patients in in 2 southern Italian regions (Calabria and Puglia). Methods: A pilot project, denominated ANDROMEDA (ANalysis of cytOgenetics alteRatiOn in the MyEloDysplAstic syndromes) was developed in 17 centers to offer a service of conventional cytogenetic analysis for all consecutive patients undergoing diagnostic evaluation for cytopenia and suspected MDS between January 1 and December 31, 2011. The study conformed to the ethical standards set out in the Declaration of Helsinki and was approved by institutional review boards at each participating center. Patients were required to provide their written informed consent. Clinical characteristics of patients and bone marrow morphology, iron staining and histology were registered. Bone marrow samples were centralized for standard cytogenetic studies and fluorescence in situ hybridization to two dedicated genetics laboratories (one for each region), blind to patients' data. Results: Two hundred and thirty-five patients were evaluated and MDS diagnosis was confirmed in 220 cases (88. 3%), according to WHO criteria. The overall incidence of clonal chromosome abnormalities detected by conventional analysis was 36. 9%. Single abnormalities included +8 (13 cases, 5. 8%), del(5q) (12 cases, 5. 4%), –Y (11 cases, 5. 0%) and del(7)/-7 (4 cases, 1. 8%). Complex karyotypes were detected in 18 (8. 1%) cases. Among all cases only 10 (4. 5%) bone marrow samples were not evaluable for cytogenetic analysis. FISH revealed additional abnormalities not identified by conventional analysis only in 3 (1. 3%) out of 72 cases. Patients were classified in WHO subtypes: 39. 2% refractory cytopenia with unilineage dysplasia (RCUD), 1. 5% refractory anemia with ring sideroblasts (RARS), 32. 5% refractory cytopenia with multilineage (RCMD), 10. 8% refractory anemia with excess of blast-1 (RAEB-1), 9. 3% refractory anemia with excess of blast-2 (RAEB-2), 4. 1% MDS with deletion 5q (MDS 5q-) and 2. 6% MDS unclassifiable (MDS-U). Conclusions: These preliminary results demonstrate that the incidence of abnormal karyotype patterns and WHO subgroups in MDS patients in Southern Italy is comparable with that described in other geographical areas. It is confirmed that conventional cytogenetic analysis is a standard in the diagnostic workup of MDS of patients with a suspected myeloid malignancy in order to identify primary abnormalities and prognostic models. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A method for simultaneous study of the karyotype, morphology, and immunologic phenotype of mitotic cells in hematologic malignancies

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 1116-1122 ◽  
Author(s):  
L Teerenhovi ◽  
S Knuutila ◽  
M Ekblom ◽  
L Rossi ◽  
GH Borgstrom ◽  
...  
Keyword(s):  
Cytogenetic Analysis ◽  
Intact Cell ◽  
Hematologic Malignancies ◽  
Sudan Black B ◽  
Conventional Cytogenetic Analysis ◽  
Glass Slides ◽  
Hypotonic Treatment ◽  
Simultaneous Study ◽  
Karyotype Morphology ◽  
Mitotic Cells

Abstract A major problem in the cytogenetic analysis of hematologic neoplasms has been an inability to identify the cell from which the chromosomes were obtained. We describe a procedure that allows simultaneous analysis of karyotype and cell cytology in mitotic cells. The method differs from conventional cytogenetic analysis in that after mild hypotonic treatment, the cells are cytocentrifuged onto glass slides. In mitotic cells, this procedure often results in adequate spread of the chromosomes within the intact cell membrane. The cytoplasmic structure also remains intact, so that cytologic preparations are of good quality. Morphologic and immunologic identification of mitotic cells can be done using routine hematologic stains, such as Giemsa or Sudan black B, and various antisera using immunofluorescence techniques. The chromosomes can be simultaneously analyzed either without banding on slides stained with Giemsa or with Q-banding on slides stained with immunofluorescence techniques. Identification of numerical and structural karyotype aberrations thus is possible in morphologically identified cells.

The Utility of Peripheral Blood FISH in the Quantitation of BCR/ABL in CML Patients on Imatinib Mesylate: A Comparison with Bone Marrow FISH and Conventional Cytogenetics.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2942-2942
Author(s):  
Samar Issa ◽  
Duncan Holdsworth ◽  
Paul Oei ◽  
Peter J. Browett
Keyword(s):  
Bone Marrow ◽  
Imatinib Mesylate ◽  
Peripheral Blood ◽  
Cytogenetic Analysis ◽  
Fusion Gene ◽  
Chronic Phase ◽  
Conventional Cytogenetic Analysis ◽  
The Mean ◽  
Conventional Cytogenetics ◽  
Mean Differences

Abstract The hallmark of CML is the BCR/ABL fusion gene that is usually formed as a result of the t(9;22) translocation. Conventional cytogenetic analysis has been the standard method for monitoring the Philadelphia (Ph) chromosome, however evaluation of the BCR/ABL fusion gene using interphase Fluorescence in situHybridisation (FISH) on peripheral blood may allow more frequent and less invasive follow up of CML patients. The objective of this study was to compare the utility of peripheral blood FISH versus bone marrow FISH and conventional cytogenetics in patients with CML following treatment with Imatinib mesylate. 61 sets of peripheral blood and bone marrow aspirate samples from 33 Ph positive chronic phase CML patients receiving treatment with Imatinib mesylate were assessed from December 2002 to February 2004. Bone marrow samples were processed by standard cytogenetic procedures and G-banded analysis of at least 20 metaphases per sample was performed. Interphase FISH on non selected peripheral blood and bone marrow samples was carried out by scoring positive signals in 600 nuclei in each sample using BCR/ABL dual fusion or extra signal probes (Vysis). Bland and Altman plots were constructed to assess the level of agreement between the tests and the mean differences (with 95% confidence intervals) were determined. 13 of the 33 patients studied were male and 21 (64%) of the patients were analyzed at more than one timepoint. Although there was good agreement of peripheral blood FISH with bone marrow FISH and bone marrow cytogenetics in monitoring changes in the level of Ph positive cells following therapy, there were statistically significant differences in the agreement between the percentage levels of BCR/ABL positive cells between bone marrow cytogenetics and bone marrow and peripheral blood FISH. Cytogenetic analysis revealed significantly higher levels of BCR/ABL positive cells when compared to both peripheral blood FISH [9% (95% CI 4.6, 14.1), p=0.013] and bone marrow FISH [5% (95% CI 1.7, 7.8, p=0.013)]. The mean difference in the percentages of the Ph positive cells measured by bone marrow FISH exceeded the peripheral blood FISH by 5% (95% CI 1.0, 8.1, p=0.037). There was a significant relationship between the differences observed and the actual percentage level of BCR/ABL positive cells (P&lt;0.001) with most of the discrepancy being driven by tests with BCR/ABL positive cells levels between 10 and 90%. In this subgroup, the cytogenetic tests were significantly higher [mean level 34% (95% CI 26, 45), p&lt;0.001] than peripheral blood FISH and 23% (95% CI 13, 33, p&lt;0.001) higher than bone marrow FISH. These observed differences may relate to the analysis of non-dividing cells in the FISH studies, including the assessment of Ph negative T lymphocytes in the peripheral blood, and need to be considered when monitoring patients by peripheral blood FISH studies alone. Figure Figure

Clonal Cells Detected by Conventional Cytogenetic Analysis Correlates with Bone Marrow Blast Percentage and Progression Free Survival Into Acute Leukemia In Myelodysplastic Syndromes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2935-2935
Author(s):  
Miyoung Kim ◽  
Cha Ja She ◽  
Sang Mee Hwang ◽  
Sung-Soo Yoon ◽  
Byoung Kook Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factors ◽  
Cytogenetic Analysis ◽  
Chromosomal Abnormalities ◽  
Progression Free Survival ◽  
Bone Marrow Blast ◽  
Free Survival ◽  
Conventional Cytogenetic Analysis ◽  
Cell Percentage ◽  
Clonal Abnormalities

Abstract Abstract 2935 Introduction: Chromosomal abnormalities not only demonstrate the clonality of the disease, but also help to predict the outcome of the patients in MDS. While IPSS suggests conventional cytogenetic analysis as a standard method in detecting clonal abnormalities in MDS, FISH is widely used due to its ability to detect minor clones and to quantitate the clonal abnormalities. In this study, we compared the results of conventional cytogenetic analysis and FISH, and investigated their different prognostic impact in MDS. Materials and Methods: The study included 129 MDS patients composed of 10 RA, 5 RARS, 15 RCMD, 39 RAEB-1, 33 RAEB-2 and 5 MDS, U (WHO classification, 2001). A standard protocol was used to perform conventional cytogenetic analysis (G-banding). Interphase FISH was performed to detect any abnormalities of chromosomes 5, 7, 8, 20 and 1. The result was analyzed as per the manufacturer¡&hibar;s instructions and recorded according to ISCN (2005) criteria. Result: The incidence of −5/5q, −7/7q, +8, −20q and +1q were 13.2%, 14.0%, 19.4%, 7.0% and 7.8%, respectively. Among them, FISH detected occult abnormalities which were not detected in conventional cytogenetic analysis in 1.6%, 3.1%, 5.4%, 1.6% and 5.4%, respectively. Overall, FISH detected occult abnormalities in 18.6% of the patients (24/129), and IPSS grouping was changed in 4.9% (6/129: 1 Low to Int-1; 4 Int-1 to Int-2; 1 Int-2 to High). The abnormalities in −5/5q, −7/7q and +1q were more common with other chromosomal abnormalities, whereas the abnormalities in +8 and −20q were more common as a sole abnormality. The quantity of clonal cells for each chromosome detected in conventional cytogenetic analysis did not correlate with the quantity of clonal cells detected in FISH. The presence of clonal cells either in conventional cytogenetic analysis or in FISH did not correlate with prognostic factors included in IPSS. However, the clonal cell percentage detected in conventional cytogenetic analysis was higher in patients with >5% bone marrow blasts than those with <5% (79.1% vs. 57.9%, p=.013). The clonal cell percentage detected in FISH did not show any relationship with IPSS factors including bone marrow blast percentage. Multivariate analysis showed the presence of clonal cells in conventional cytogenetic analysis were independent prognostic factors in predicting progression free survival into acute leukemia in this patient group (p=.038). Conclusion: FISH is advantageous in identifying cryptic cytogenetic abnormalities which could be overlooked in conventional cytogenetic analysis, and can change the IPSS risk grouping in MDS patients. The quantity of clonal cells detected in conventional cytogenetic analysis correlates with bone marrow blast percentage, whereas the quantity of clonal cells detected in FISH does not. Blasts possess higher proliferating activity than maturing hematopoietic precursors, thus they are more likely to form metaphase required in conventional cytognetic analysis. In contrast, the FISH results performed on non-dividing, interphase cells might reflect the true quantity of clonality both in blasts and maturing hematopoietic precursors. The relationship between the quantity of clonal cells and bone marrow blast percentage, and the prognostic significance of the presence of clonality suggest the novel diagnostic utility of conventional cytogenetic analysis in MDS. Disclosures: No relevant conflicts of interest to declare.

SNP/CGH Microarray Analysis in MDS: Correlation with Conventional Cytogenetic, FISH and Flow Cytometry Findings

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5592-5592
Author(s):  
Barbara Katharina Zehentner ◽  
Lisa Eidenschink Brodersen ◽  
Christine F Stephenson ◽  
Jevon Cutler ◽  
Monica E. de Baca ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Microarray Analysis ◽  
Cytogenetic Analysis ◽  
Fish Analysis ◽  
Employment Equity ◽  
Conventional Cytogenetic Analysis ◽  
Flow Cytometric ◽  
Equity Ownership ◽  
Gains And Losses

Abstract Background: Single nucleotide polymorphism (SNP) and comparative genomic hybridization (CGH) microarray analysis is a powerful tool to assess myelodysplastic bone marrow specimens for the presence of genomic gains and losses as well as loss of heterozygosity (LOH) (reviewed by Nybakken & Bagg, JMD 2014). Its application can be a valuable addition to conventional cytogenetic analysis and may be superior to FISH testing for MDS assessment. Currently, microarray analysis does not have widespread use in an MDS work-up. Several groups have demonstrated that flow cytometric analysis can detect phenotypic aberrations in bone marrow aspirates with cytopenias with more abnormalities identified in patients with poor prognosis or with multiple genotypic abnormalities (Loken et al. 2008; Cutler et al. 2011; van de Loosdrecht et al. 2013). In this study SNP microarray results were compared with conventional cytogenetic and MDS panel FISH findings as well as phenotypic abnormalities detected by flow cytometry. Patients and Methods: 185 bone marrow aspirate specimens submitted to our laboratory for MDS work-up were analyzed by SNP/CGH studies. 36 of these (19.5%) were positive by SNP/CGH microarray analysis. 32 of the positive microarray cases (88.9%) were also analyzed by conventional cytogenetic studies, 35 (97.2%) by MDS FISH panel (5p, 7q, +8, -17p, -20q) and 31 (86.1%) were assessed by multidimensional flow cytometry (FCM) and were assigned an FCSS score (Wells et al. 2003). Results: Of the specimens in which the SNP/CGH array demonstrated genotypic abnormalities, 11/32 (34.4%) were negative by conventional cytogenetic analysis while 12/35 (34.3%) showed no abnormalities by MDS FISH panel analysis. SNP/CGH analysis revealed additional chromosomal gains and losses in 18/32 (56%) in comparison to cytogenetic analysis and in 22/35 (63%) in comparison to FISH analysis. Loss of Heterozygosity regions were detected in 28/36 cases (78%) with 96.4% (27/28) of these being larger than 2 Mb and 53% (19/28) spanning a significant chromosomal region (e.g. 1p, 5q, 7q and 17p) with known oncogenic and other MDS related genes. In 10/32 cases (31%), microarray analysis was able to characterize the origin of marker chromosome material, previously reported with unknown identity by conventional cytogenetic analysis. In an additional subset of 10 out of 32 cases (31%), cytogenetic analysis was able to either characterize balanced translocations or low level sub-clonal abnormalities not identified by microarray analysis alone. In 11/36 (31%) microarray analysis was able to detect clonal heterogeneity and evolution. In none of the specimens did FISH analysis detected abnormalities not revealed by microarray analysis. Flow cytometry performed on 31 of the array positive specimens revealed 6 to have >20% abnormal myeloid progenitor cells (classified as AML) while 23 the remaining 25 cases showed phenotypic abnormalities consistent with MDS (FCSS ranging from 1-6). In two specimens with a FCSS of 0, LOH regions on 16q or 1p and 21q were found, respectively, without the presence of numerical aberrations. A FCSS score of 1 with minimal phenotypic abnormalities (n=3), was comprised of one specimen with del(5q), one with LOH of 7q and one with trisomy 8, 1p loss and 1q gain. Specimens with an FCSS of 2 (n=7) showed only one specimen classified as complex (5 or more abnormalities). The two FCSS =3 specimens showed del(5q) with del(12p) and several LOH regions, not complex findings. One of the 4 specimen with FCSS = 4 was classified as complex while the other 3 specimens showed monosomy 7, LOH of 7q or LOH of 1p, respectively. Genotypic abnormalities were also related to phenotypic abnormalities in 4/7 (57%) specimens in the FCSS = 5/6 category which revealed complex microarray findings. Half (3/6) of the AML class had complex findings as well. Conclusions: These results emphasize the additional value that CGH/SNP microarray analysis adds to conventional cytogenetic analysis. Our dataset confirms that FISH studies do not provide additional information for MDS specimens positive by cytogenetic and/or microarray analysis. Most importantly, a high correlation between our phenotypic flow cytometric scoring system for myeloid abnormalities and microarray findings has been identified. Higher flow cytometric abnormality scores correlate with increasing complexity of genomic abnormalities. Disclosures Zehentner: HematoLogics Inc.: Employment, Equity Ownership. Brodersen:Hematologics Inc.: Employment. Stephenson:Hematologics Inc.: Employment. de Baca:Hematologics Inc.: Employment. Menssen:Hematologics Inc.: Employment. Hammock:Hematologics Inc.: Employment. Johnson:Hematologics Inc.: Employment. Hartmann:Hematologics Inc.: Employment. Loken:Hematologics Inc.: Employment, Equity Ownership. Wells:HematoLogics Inc.: Employment, Equity Ownership.

Comparison of Outcomes of Unrelated Bone Marrow and Umbilical Cord Blood Transplants in Children with Hematologic Malignancies: Single Center Study in Korea.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5164-5164
Author(s):  
Nak-Gyun Chung ◽  
Bin Cho ◽  
Young-Shil Park ◽  
Dae-Chul Jeong ◽  
Pil-Sang Jang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematologic Malignancies ◽  
Bone Marrow Transplants ◽  
Single Center ◽  
Hematopoietic Stem ◽  
Single Center Study ◽  
Center Study

Abstract In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBT) or bone marrow transplants, 102 children with hematologic malignancies transplanted with unrelated umbilical cord blood (n=35, M:F=21:14, median age 4 years) or unrelated bone marrow transplants (UBMT) (n= 67, M:F=49:18, median age 9 years) were analyzed in a retrospective single center study (between Aug. 1997 and Dec. 2003 in the Catholic Hematopoietic Stem Cell Transplantation Center of Korea). HLA mismatches were defined by serology for class I and molecular typing for DRB1. The donor was HLA mismatched in 94% of UCBTs (33 of 35 UCBT) and in 0 % of UBMT. Non-adjusted estimates of 2-year event-free survival rates were 46 % and 57 %, respectively (P > 0.2). Engraftment failures of donor cells occurred in 17 % (6 out of 35) of UCBT and in 6 % (4 out of 67) of UBMT. Grade >= III acute GVHDs developed in 3 out of 29 (10 %) engrafted patients who underwent UCBT and in 17 out of 63 (27 %) engrafted patients who underwent UBMT. Early TRM at day 100 was 31 % (11 out of 35) for UCBT and 22 % (12 out of 67) for UBMTs. Within post-transplant month 3, CMV infections occurred in 37 % of UCBT and 54 % of UBMT, but most of them did not progress to CMV disease due to early ganciclovir treatment. Chronic GVHD developed in 2 out of 22 (9 %) patients who underwent UCBT and in 15 out of 49 (31 %) patients underwent UBMT. In conclusion, the use of UCBT as a source of hematopoietic stem cells is a reasonable option for children with hematologic malignancies lacking an acceptable, matched unrelated marrow donor.

scholarly journals Therapy-Related Pro-B Cell Acute Lymphoblastic Leukemia: Report of Two Patients with MLL Amplification

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4911-4911
Author(s):  
Frederick Racke ◽  
Carol Cole ◽  
Nyla A. Heerema
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cytogenetic Analysis ◽  
Topoisomerase Ii ◽  
Bone Marrow Examination ◽  
Hematologic Malignancies ◽  
Fish Analysis ◽  
Dna Topoisomerase Ii ◽  
Acute Leukemias ◽  
Dna Topoisomerase

Abstract Abstract 4911 Recent advances in cancer treatment have led to an ever increasing number of cancer survivors. Unfortunately, a small fraction of these patients develop secondary hematologic malignancies as a consequence of their exposure to genotoxic anti-cancer regimens. Most of these are myeloid malignancies, therapy-related acute myeloid leukemia (t-AML) or myelodysplasia (t-MDS). Current classification schemes separate therapy-related myeloid disorders into two classes, those related to prior exposure to alkylating agents or radiation and those with prior exposure to DNA topoisomerase II inhibitors. The alkylating/radiotherapy group often contain chromosomal abnormalities involving chromosomes 5 and 7. In contrast, those with DNA topoisomerase II inhibitor exposure frequently possess chromosomal translocations involving chromosome 11q23, where the MLL gene locus resides. MLL, or “mixed lineage leukemia”, is also frequently rearranged in lymphoblastic leukemias and mixed phenotype acute leukemias. Interestingly, MLL also can be altered in myeloid disease through partial tandem duplication or amplification of the genomic region encompassing MLL [amp(MLL)]. Amp(MLL) of an unrearranged MLL locus has also been described in therapy-related myeloid disease. Recently, there has been a growing appreciation that therapy-related leukemias are not limited to the myeloid lineage and that therapy-related acute lymphoblastic leukemias (t-ALL) make up a small but significant percentage of therapy-related acute leukemias. Translocations involving the MLL locus have been found in a high percentage of t-ALLs. However, to our knowledge, amp(MLL) has not been reported previously in t-ALL. Herein we report 2 cases of ALL following chemotherapy for other malignancies that showed complex karyotypic abnormalities and distinct MLL amplification by FISH analysis. Patient 1 is an 80 year old male with a past medical history significant for a stage IV diffuse large B cell lymphoma two years prior. The patient received 8 cycles of R-CHOP chemotherapy and achieved a complete remission. One year later, he had a recurrence and was treated with 7 cycles of RICE chemotherapy. Eleven months later, he presented with leukopenia. A bone marrow examination revealed involvement by B cell ALL. Cytogenetic analysis showed a hypodiploid complex karyotype which included a homogeneously staining region (hsr) at chr11(q23). Metaphase FISH analysis showed amp(MLL) in the hsr. Patient 2 is a 62 year old male who five years prior had been diagnosed with a pleiomorphic sarcoma of the left hip. The patient received four cycles of doxorubicin and ifosfamide as well as radiation therapy. The patient remained well for five years but then presented with bleeding and a petechial rash. A complete blood count revealed anemia and thrombocytopenia. A bone marrow examination was performed which showed involvement by B cell ALL. Cytogenetic analysis showed multiple numerical and structural abnormalities including an hsr at chr11(q23) in all lines as well as a second hsr in two sidelines. Metaphase FISH analysis showed amp(MLL) in all cells and in both hsrs. Immunophenotypic analysis showed both cases to express a Pro-B cell (CD10-) phenotype with aberrant myeloid antigen expression. Frequent molecular perturbation makes the MLL locus one of the most common genetic targets in hematologic malignancies, particular in therapy-related neoplasms. The majority of MLL genetic alterations result in translocations involving the MLL gene. These translocations result in fusion proteins with heterologous functions of MLL that result in a block of differentiation. Similarly, amp(MLL), while not creating an abnormal fusion protein involving MLL, also is considered to be a “gain of function” mutation caused by increased expression of MLL. There seems to be an increased frequency of aml(MLL) in therapy-related myeloid disorders. In summary, we report, to our knowledge, the first cases of therapy-related pro B cell (CD10-) ALL associated with amp(MLL). The shared phenotype between B cell ALLs with MLL rearrangements and amp(MLL) suggests that both lesions may exert similar influences on the transcriptional programs of these leukemias. This observation extends the family of MLL-associated and therapy-related hematologic disorders. Disclosures: No relevant conflicts of interest to declare.

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