Significance of cytogenetic abnormalities in acute myeloid leukaemia (original) (raw)
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Evaluation of the cytogenetic profile in patients with acute leukaemia
Polish Journal of Pathology
Acute leukaemia (AL) is a heterogeneous neoplastic disease that occurs by the growth of abnormal lymphoid and myeloid cells in the bone marrow and blood leading to acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL). Conventional cytogenetics is a characteristic technique to hunch chromosomal abnormalities, it helps in the diagnosis and therapeutic approach of the disease by the molecular cytogenetics technique of fluorescence in situ hybridization (FISH). Chromosomal abnormalities in AL are performed by karyotyping to confirm specific chromosomal abnormalities using FISH. The descriptive study included 42 clinically diagnosed AL patients. Karyotyping analysis was performed using the standard Giemsa banding procedure. To confirm specific chromosomal abnormalities and all culture failure (CF) cases, FISH was done. Among 42 cases, 29 (69.4%) males and 13 (30.9%) females, AML comprised 22 (52.38%) cases, ALL 14 (33.33%) cases, and AL 6 (14.2%) cases. Normal karyotype was found in 18 (42.85%), abnormal karyotype in 16 (39.09%), and 8 (19.09%) were CF. Specific abnormalities of t(15;17), hyperdiploidy; t(3;3) with monosomy 7 in; del(9q22); del(2p); del(17p); del(Xq); 1~2 dmin; der(3); +11, +13 and composite karyotype. Hypodiploidy was strongly associated with AL, which signifies the loss of chromosomes causing potential risk. Composite karyotype, rare t(3;3) double minutes, +11,+13, del(9q), and del(Xq) were the novel findings reported in the South Canara region of Karnataka. Despite other molecular techniques, conventional cytogenetics remains the baseline in the diagnosis of malignancies.
Leukemia, 2004
The aim of this study was to compare the pattern of karyotype abnormalities of therapy-related acute myeloid leukemia (t-AML) (n ¼ 93) with de novo AML (n ¼ 1091), and to evaluate their impact on prognosis. Favorable, intermediate, and unfavorable cytogenetics were observed in 25.8, 28.0, and 46.2% of t-AML, and in 22.2, 57.3, and 20.4% of de novo AML. The median overall survival (OS) was shorter in t-AML than in de novo AML (10 vs 15 months, P ¼ 0.0007). Favorable and unfavorable cytogenetics had a prognostic impact with respect to OS in both t-AML (P ¼ 0.001 and 0.0001) and de novo AML (Po0.0001 and o0.0001). To define the overall prognostic impact of cytogenetics and t-AML, a multivariate Cox's regression analysis was performed for OS with favorable cytogenetics, unfavorable cytogenetics, t-AML, age, and white blood cell (WBC) count as covariates. All parameters proved to be independently related to OS (P ¼ 0.001 for t-AML, Po0.0001 for all other parameters). Within patients with t-AML, there were significant correlations between OS and both unfavorable (Po0.0001) and favorable cytogenetics (P ¼ 0.001), while age and WBC count had no impact on OS. In conclusion, these data indicate that cytogenetics are an important prognostic parameter in t-AML. Furthermore, t-AML is an unfavorable factor independent of cytogenetics with respect to survival.
Correlation of karyotype with clinical features in acute lymphoblastic leukemia
Cancer research, 1982
We studied the clinical and karyotypic features of 50 patients with acute lymphoblastic leukemia, including 33 American and 17 Japanese patients, at two institutions. Clonal chromosome abnormalities were found in 39 of the 50 patients (78%) at diagnosis. Eleven patients had diploidy (N patients). Among the 39 aneuploid patients, 17 had pseudodiploidy (A1 patients), eight had hyperdiploidy with 47 to 49 chromosomes (A2 patients), nine had hyperdiploidy with 50 to 59 chromosomes (A3 patients), and five had other chromosome abnormalities. Of 14 patients whose chromosomes were also studied at relapse, eight had karyotypic progression, five had abnormalities identical or similar to those observed at diagnosis, and one had a change of karyotype from diploidy to aneuploidy. The median age and the median WBC of A1 patients were higher than those of any other group of patients, although one-third of the patients had WBC below 20 x 10(3)/microliters, and they often had leukemic cells of T-cel...
2021
Conventional cytogenetic analysis (CCA) - a relatively dated method, still holds a valued position in the diagnostic and evaluation algorithm of hematological diseases despite the constantly evolving genomic era. Hereby we focus on the heterogeneous Acute myeloid leukemia (AML) with a diagnostic process that requires routine CCA on bone marrow samples. We have conducted a retrospective analysis on patients with current diagnosis AML who underwent CCA in the Laboratory of Medical genetics, UMHAT “St. Marina”, Varna, for eleven years – 01.2010 through 12.2020. Karyotyping was performed with GTG-banding technique in accordance with the International System for Human Cytogenomic Nomenclature. We have assessed 723 samples of 422 patients – 225 (53.3%) males, 197 (46.7%) females, and 11 (2.6%) of all - children. 125 (29.6%) patients were tested more than once in order to monitor their treatment response and overall disease evolution. Out of 606 successful CCA with a resolution mode 150-200 bands, karyotype was normal in 369 (60.9%) and abnormal in 237 (39.1%). The latter was mainly presented by complex karyotype in 83 (13.7%), trisomy 8 in 14 (2.3%), inv(16;16) or t(16;16) in 13 (2.1%) and t(8;21) in 10 (1.7%). According to the European Leukemia Net (2017) risk stratification, 23 (3.8%) belonged to the favourable, 469 (77.4%) - to the intermediate, normal karyotype included, and 105 (17.3%) - to the adverse risk group. AML comprised 29.6% of all bone marrow samples for the period – a share steadily growing through the years for both new and re-assessed patients. CCA is an essential part of the AML evaluation process since cytogenetic findings carry certain prognostic and diagnostic values. Noteworthy limitations in terms of resolution, turnaround time and possible lack of success lead to a marked necessity of subsidiary molecular-genetic method.
Haematology Journal of Bangladesh
Background: Cytogenetic analysis performed at diagnosis is considered to be the most important prognostic factor in AML. Objective: The purpose of this study was to observe the pattern of cytogenetic abnormalities in adult patients with de novo AML. Method: Total fifty-two newly diagnosed de novo AML patients were selected for the study. Six cytogenetic abnormalities including t(8;21), t(15;17), inv(16), BCR-ABL1, FLT3-ITD & NPM1 mutations were detected by Real-Time PCR. Results: In this study, 36 (69.2%) patients showed different cytogenetic abnormalities. The t(15;17) was found to be the most common. t(15;17), t(8;21) and inv(16) were found only in M3, M2 and M4 FAB subtypes, respectively. Significant association was found with increasing age and cytogenetic risk groups. BCR-ABL1 mutation showed significant relation with increased age. FLT3-ITD mutation showed significant association with increased WBC count and inv16 was significantly associated with relatively less bone marrow b...
Blood, 2011
In acute myeloid leukemia (AML) the subset with complex karyotype (CK) is traditionally regarded as the worst prognostic group. However, ≥ 3, ≥ 4, or ≥ 5 abnormalities have been variably used for its definition. Recently, monosomal karyotype (MSK) was suggested to indicate an even inferior outcome. We tested which definition fits best to identify the most unfavorable subgroup. After excluding patients with t(15;17)/PML-RARA, t(8;21)/RUNX1-RUNX1T1, inv (16)/t(16;16)/CBFB-MYH11, and normal karyotype, 824 patients with AML with cytogenetic abnormalities were analyzed. Patients with MSK or CK defined as ≥ 3, ≥ 4, or ≥ 5 abnormalities showed an inferior overall survival compared with the respective remaining patients not fulfilling these criteria (for all, P < .001). Hazard ratios were 1.93, 1.68, 1.94, and 1.92. CK ≥ 4 as a single parameter identified the largest proportion of patients with very poor risk. However, combining CK ≥ 4 and MSK detected an even larger number of patients w...
Cytogenetic Profile of Monosomal Karyotype in Adult Acute Myeloid Leukemia
Cytogenetic abnormalities at diagnosis are important prognostic indicators in acute myeloid leukemia (AML). AML is categorized into 3 risk groups according to cytogenetic abnormalities; favorable, intermediate, and unfavorable. A new cytogenetic risk group called the monosomal karyotype (MK) had been identified in AML with unfavorable-risk cytogenetics. The MK was reported to be associated with a dismal prognosis. The objective of this retrospective study was to analyze the type of chromosomal abnormalities found in adult AML patients with MK at diagnosis.
Evaluation of Cytogenetic Abnormalities in Patients with Acute Lymphoblastic Leukemia
Indian Journal of Hematology and Blood Transfusion, 2019
Acute lymphoblastic leukemia (ALL) accounts for 20% of all adult leukemias and is the most common leukemia during childhood (80%). We present data on cytogenetics of ALL from a tertiary centre in India correlating it with clinical factors. Karyotyping of bone marrow samples of 204 patients with newly diagnosed ALL was performed with standard G-banding technique. Clinical data of patients was obtained from case records. Survival was estimated using Kaplan-Meir curves and compared by the log-rank test. Univariate and multivariate analysis was done for survival with age, sex, immunophenotype, hyperleukocytosis, risk type, remission status and cytogenetics. The most common karyotypes observed were normal in 39.7% (N = 81), hyperdiploidy in 12.7% (N = 26), t(9;22) in 4.4% (N = 9), t(1;19) in 3.9% (N = 8). Adults with ALL had worse survival compared with pediatric patients (HR 3.62; 2.03-6.45 95% CI, p \ 0.001). Patients not in morphologic remission after induction chemotherapy fared poorly (HR 4.86; 2.67-8.84 95% CI, p \ 0.001). Patients with favourable cytogenetics had better overall survival (HR 0.36; 0.12-1.05 95% CI, p \ 0.05). On multivariate analysis, achievement of morphologic remission emerged as single most significant predictor of survival (p \ 0.001). MLL gene rearrangement and t(12;21) were seen less commonly as compared to Western data. However, incidence rates of various cytogenetic abnormalities were similar to that reported from other centres from India. Age, morphologic remission at end of induction chemotherapy and favourable cytogenetics correlated significantly with survival.
British Journal of Haematology, 2001
Haematological, immunophenotypic and cytogenetic characteristics were analysed in 241 patients with acute myeloid leukaemia (AML) M0, including 58 children. Children , 3 years and adults between 60 and 70 years of age were most frequently affected. Immunophenotyping showed a heterogeneous phenotype. Anti-myeloperoxidase was positive in about half of the patients. Cytogenetic data were available from 129 (54%) patients. A normal karyotype was found in only 24%. Most of the abnormalities were unbalanced and the chromosomes 5, 7, 8 and 11 were the most frequently affected. Survival data were available from 152 treated patients (63%). The median overall survival for all patients was 10 months, 20 months for children (n 36), 10 months for the young adult group (n 50) and 7 months for the elderly patients (n 66) (P 0´09). Karyotype was not a prognostic factor influencing survival. AML M0 shows the immunological characteristics of early progenitor cells, but the expression of the different markers and cytogenetic abnormalities is heterogeneous. The prognosis is poor compared with other de novo AML and similar to that of AML with multilineage dysplasia or AML following myelodysplastic syndromes.