scholarly journals Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2982-2988 ◽  
Author(s):  
CM Rubin ◽  
DC Arthur ◽  
WG Woods ◽  
BJ Lange ◽  
PC Nowell ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Alkylating Agents ◽  
Normal Karyotype ◽  
Chromosome 11 ◽  
Prior Therapy ◽  
11Q23 Abnormalities ◽  
Acute Myeloid

Abstract We have studied 20 children with therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were 3 months to 16 years old at diagnosis of their primary neoplasm and 1 to 24 years old at diagnosis of their secondary neoplasm. The median interval from initial treatment for the first malignancy to diagnosis of therapy- related MDS or AML was 46 months (range, 12 to 116 months). Twelve patients had chromosomal abnormalities resulting in loss of material from the long arm of chromosomes 5 and/or 7, three patients had abnormalities of chromosome 11 band q23, one patient had both classes of abnormalities, three patients had other abnormalities, and one patient had a normal karyotype. Ten of 12 patients with chromosome 5 and/or 7 abnormalities had been exposed to an alkylating agent, and two of three patients with 11q23 abnormalities had been exposed to an epipodophyllotoxin. The patient with both classes of abnormalities had been exposed to both types of therapy. We conclude that abnormalities of chromosomes 5 and/or 7 are common in children with therapy-related MDS or AML. The proposed relationships between exposure to alkylating agents and abnormalities of chromosomes 5 and/or 7 and between exposure to epipodophyllotoxins and abnormalities of 11q23 are supported in this pediatric series.

scholarly journals Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy

Blood ◽  
1991 ◽  
Vol 78 (11) ◽  
pp. 2982-2988 ◽  
Author(s):  
CM Rubin ◽  
DC Arthur ◽  
WG Woods ◽  
BJ Lange ◽  
PC Nowell ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Alkylating Agents ◽  
Normal Karyotype ◽  
Chromosome 11 ◽  
Prior Therapy ◽  
11Q23 Abnormalities ◽  
Acute Myeloid

We have studied 20 children with therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were 3 months to 16 years old at diagnosis of their primary neoplasm and 1 to 24 years old at diagnosis of their secondary neoplasm. The median interval from initial treatment for the first malignancy to diagnosis of therapy- related MDS or AML was 46 months (range, 12 to 116 months). Twelve patients had chromosomal abnormalities resulting in loss of material from the long arm of chromosomes 5 and/or 7, three patients had abnormalities of chromosome 11 band q23, one patient had both classes of abnormalities, three patients had other abnormalities, and one patient had a normal karyotype. Ten of 12 patients with chromosome 5 and/or 7 abnormalities had been exposed to an alkylating agent, and two of three patients with 11q23 abnormalities had been exposed to an epipodophyllotoxin. The patient with both classes of abnormalities had been exposed to both types of therapy. We conclude that abnormalities of chromosomes 5 and/or 7 are common in children with therapy-related MDS or AML. The proposed relationships between exposure to alkylating agents and abnormalities of chromosomes 5 and/or 7 and between exposure to epipodophyllotoxins and abnormalities of 11q23 are supported in this pediatric series.

P-194 Successful azacitidine based treatment of therapy related myelodysplastic syndrome with normal karyotype occurred after acute myeloid leukemia

2013 ◽  
Vol 37 ◽  
pp. S110-S111 ◽  
Author(s):  
F. Saltarelli ◽  
C. Tatarelli ◽  
M.A. Aloe Spiriti ◽  
V. Naso ◽  
M.P. Bianchi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Acute Myeloid

scholarly journals The t(11;16)(q23;p13) Translocation in Myelodysplastic Syndrome Fuses the MLL Gene to the CBP Gene

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 3945-3950 ◽  
Author(s):  
Tomohiko Taki ◽  
Masahiro Sako ◽  
Masahiro Tsuchida ◽  
Yasuhide Hayashi
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Dna Methyltransferase ◽  
Creb Binding Protein ◽  
Mll Gene ◽  
Recurrent Translocation ◽  
Coactivator Protein ◽  
11Q23 Abnormalities ◽  
Acute Myeloid

Abstract The recurrent translocation t(11; 16)(q23; p13) has been reported to be associated with therapy-related acute leukemia. The MLL gene involved in other 11q23 abnormalities was also rearranged by this translocation. We analyzed two patients with myelodysplastic syndrome with t(11; 16) and showed that the MLL gene on 11q23 was fused with CREB-binding protein (CBP) gene on 16p13 in these patients. The CBP gene encodes a transcriptional adaptor/coactivator protein and it is mutated in patients with Rubinstein-Taybi syndrome. The CBP gene is also involved in acute myeloid leukemia (AML) with t(8; 16)(p11; p13). In-frame MLL-CBP fusion transcripts combine the MLL AT-hook motifs and DNA methyltransferase homology region with a largely intact CBP. Our results combined with the finding of the MOZ-CBP fusion in t(8; 16)-AML suggest that the CBP gene may be associated with leukemogenesis through translocations.

MYC Expression Is Prognostic in Therapy Related Acute Myeloid Leukemia (AML) and AML with Myelodysplastic Syndrome (MDS)-Related Changes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5334-5334
Author(s):  
Maro Ohanian ◽  
Uri Rozovski ◽  
Hagop M. Kantarjian ◽  
Sanam Loghavi ◽  
Yang O. Huh ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Myelodysplastic Syndrome ◽  
Clinical Significance ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Newly Diagnosed ◽  
Expression Levels ◽  
Previously Treated ◽  
Acute Myeloid

Abstract Background: MYC mRNA overexpression has been described in acute myeloid leukemia (AML), but no studies have assessed MYC protein expression in AML where its clinical significance is unknown. In this study our aim is to assess MYC protein expression across all AML subtypes and explore its prognostic value in in a subset of patients (pts) with particularly poor prognosis, namely those with AML with myelodysplastic syndrome (MDS)-related changes (AML-MRC) and therapy-related AML (t-AML). Characterized by unfavorable cytogenetics, the prognosis of patients with AML-MRC and t-AML is often dismal, even in patients who undergo allogeneic stem cell transplant. There is a need for further molecular characterization of AML-MRC and t-AML to identify prognostic markers to optimally risk-stratify to better guide treatment decisions in these pts. Objectives: In the current study we sought to: (1) assess MYC protein expression by immunohistochemistry (IHC) performed on bone marrow (BM) specimens of pts with all types of AML, including acute promyelocytic leukemia (APL), and myelodysplastic syndromes (MDS), and (2) explore the prognostic significance of MYC protein expression in AML-MRC and t-AML (2008 WHO criteria). Methods: MYC protein expression was assessed by IHC on BM obtained from pts with AML, APL, and MDS, and from patients without hematologic neoplasms (normal controls). MYC expression was considered positive if > 5% blasts in BM showed nuclear reactivity. For cases classified as t-AML and AML-MRC by WHO 2008, MYC expression was correlated with molecular, cytogenetic, and clinical outcome data. X-tile software was used to identify the optimal cutoff point to dichotomize pts by MYC protein expression. Results: We evaluated BM MYC expression in 306 pts during 2006-2013 with newly diagnosed AML (n=246) or APL (n=11), previously treated AML (induction failure or relapse) (n=30), MDS (n=19), AML-MRC (n=68), t-AML (n=10), and normal BM (n=11). The median age was 61 yrs (13-88) with 54% men. Normal BM showed negligible MYC expression, ≤2% positive nuclei. The median MYC expression varied across diseases: newly diagnosed AML 25% (range 0-38%), APL 50% (range 19-75%), previously treated AML 20% (range 0-80), MDS 5% (range 0-30%) (differences between groups, p=0.0001). High MYC expression correlated with high LDH (rs = 0.285, p<0.0001), WBC (rs = 0.225, p<0.0001) and BM blasts (rs 0.417, p<0.0001). Among newly diagnosed AML pts 20 had normal MYC expression ≤ 2%. MYC rearrangement by FISH was not detected in tested normal karyotype AML cases with variable MYC expression levels. MYC rearrangement by FISH was not detected in tested normal karyotype AML cases with variable MYC expression levels. The clinical significance of MYC expression was examined in 78 pts with previously untreated AML-MRC and t-AML (59% men, median age 64 years). Pts with MYC expression above a determined cutoff of 21% had a significantly worse median overall survival (OS) of 8 months compared to 17 months in those with MYC ≤ 21% (p=0.035). Disease free survival (DFS) was also inferior in pts with higher MYC expression. Median DFS was 3 months in pts with MYC >21% and 8 months for pts with MYC ≤ 21% (p=0.064). The rate of CR was 63% in pts with MYC≤ 21% and 37% in those >21%, however this difference was not statistically significant. In pts with newly diagnosed AML-MRC and t-AML, high MYC expression did not correlate with markers of proliferation (high LDH, WBC and BM blasts). Furthermore, MYC levels were similar across karyotypes: trisomy 8 (where MYC resides), complex, and core binding factors. Conclusion: MYC protein expression is a strong predictor of survival and an important biomarker of prognosis in patients with t-AML and AML-MRC. On BM IHC, pts with >21% MYC-positive blasts have an inferior OS, DFS, and remission rate than pts with ≤ 21% MYC-positive blasts. Increased MYC protein expression is independent of rearrangement status by FISH. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype

Haematologica ◽  
2009 ◽  
Vol 94 (2) ◽  
pp. 213-223 ◽  
Author(s):  
T. Akagi ◽  
S. Ogawa ◽  
M. Dugas ◽  
N. Kawamata ◽  
G. Yamamoto ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Acute Myeloid

scholarly journals Cytogenetics' impact on the prognosis of acute myeloid leukemia

2019 ◽  
Vol 11 (02) ◽  
pp. 133-137 ◽  
Author(s):  
Monika Gupta ◽  
Manoranjan Mahapatra ◽  
Renu Saxena
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Hematological Parameters ◽  
Normal Karyotype ◽  
Response To Therapy ◽  
Flow Cytometric ◽  
Risk Patients ◽  
Standard Risk ◽  
Acute Myeloid

Abstract INTRODUCTION: Acute myeloid leukemia (AML) is a group of disorders characterized by a spectrum of clinical, morphological, immunophenotypic, and associated chromosomal abnormalities. The identification of cytogenetic abnormalities at diagnosis is important for the evaluation of the response to therapy and the identification of an early reemergence of disease. MATERIALS AND METHODS: Newly diagnosed cases of AML were included in the study. Diagnosis of AML was based on morphology on bone marrow (BM) aspirates, cytochemistry, and flow cytometric immunophenotyping. Chromosomal analysis was performed on BM by short-term unstimulated cultures using standard cytogenetic technique. RESULTS: There were 25 males and 13 females with age group between 15 and 64 years. Cytogenetic analysis of these cases showed normal karyotype in 10 (26.3%) cases and abnormal karyotype in 28 (73.6%) cases. Cytogenetic finding in AML was divided into three groups: favorable risk, intermediate risk, and unfavorable risk. Patients in the standard risk group responded well to the chemotherapy while patients with intermediate and unfavorable karyotype had relapsed. CONCLUSION: We recommend that cytogenetics should be performed routinely in all cases of AML. A correlation must be done with various biochemical and hematological parameters, immunophenotyping, and BM morphology. Molecular studies must be integrated with cytogenetic studies for risk stratification at diagnosis to improve therapeutic strategies.

Homogeneously staining region (hsr) on chromosome 11 is highly specific for KMT2A amplification in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)

2019 ◽  
Vol 238 ◽  
pp. 18-22 ◽  
Author(s):  
Ali Sakhdari ◽  
Zhenya Tang ◽  
Chi Young Ok ◽  
Carlos E. Bueso-Ramos ◽  
L. Jeffrey Medeiros ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Chromosome 11 ◽  
Acute Myeloid

scholarly journals Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts

Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5583-5592 ◽  
Author(s):  
Olga Blau ◽  
Claudia Dorothea Baldus ◽  
Wolf-Karsten Hofmann ◽  
Gundula Thiel ◽  
Florian Nolte ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Mesenchymal Stromal Cells ◽  
Chromosomal Aberrations ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Genetic Alterations ◽  
Genetic Abnormalities ◽  
Acute Myeloid

Abstract Mesenchymal stromal cells (MSCs) are an essential cell type of the hematopoietic microenvironment. Concerns have been raised about the possibility that MSCs undergo malignant transformation. Several studies, including one from our own group, have shown the presence of cytogenetic abnormalities in MSCs from leukemia patients. The aim of the present study was to compare genetic aberrations in hematopoietic cells (HCs) and MSCs of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients. Cytogenetic aberrations were detected in HCs from 25 of 51 AML patients (49%) and 16 of 43 MDS patients (37%). Mutations of the FLT3 and NPM1 genes were detected in leukemic blasts in 12 (23%) and 8 (16%) AML patients, respectively. Chromosomal aberrations in MSCs were detected in 15 of 94 MDS/AML patients (16%). No chromosomal abnormalities were identified in MSCs of 36 healthy subjects. We demonstrate herein that MSCs have distinct genetic abnormalities compared with leukemic blasts. We also analyzed the main characteristics of patients with MSCs carrying chromosomal aberrations. In view of these data, the genetic alterations in MSCs may constitute a particular mechanism of leukemogenesis.

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