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 Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 37  |  Issue : 4  |  Page : 213-220

Polysomy 8 in Egyptian patients with de-novo acute myeloid leukemia


1 Department of Clinical Pathology, Ain Shams University, Cairo, Egypt
2 National Research Center, Cairo University, Giza, Egypt
3 Department of Internal Medicine, Ain Shams University, Cairo, Egypt

Date of Submission01-Apr-2012
Date of Acceptance30-Apr-2012
Date of Web Publication21-Jun-2014

Correspondence Address:
Nevine Nabil Moustafa
Internal Medicine Department, Ain Shams University, P.O. Box 12611, Abbassia, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.7123/01.EJH.0000418701.83604.d3

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  Abstract 

Background

Tetrasomy, pentasomy, and hexasomy of the entire chromosome 8 (polysomy 8) are relatively rare compared with trisomy 8, which is one of the most common recurring aberrations in myeloid hematologic malignancies. Although polysomy 8 appears to adversely influence outcome, little is known about the prognostic significance of polysomy 8 in patients with acute myeloid leukemia (AML).

Aim of the work

The aim of the present work was to study the numerical aberrations of chromosome 8 in Egyptian patients with AML and to clarify its role as a prognostic marker.

Patients and methods

The present study was carried out on 76 newly diagnosed adult patients with AML. They were attending the Hematology Department of Ain Shams University Hospitals. They were subjected to conventional cytogenetic analysis using G-banding and fluorescence in-situ hybridization using a fluorophore-labeled centromeric probe for chromosome 8.

Results

Metaphase and interphase fluorescence in-situ hybridization for detection of polysomy 8 was successfully performed on 72 samples. Patients were divided into two groups: group A comprised patients associated with polysomy 8 (20 patients; 27.8%) and group B comprised patients without polysomy 8 (52 patients; 72.2%). Group A patients had a statistically significant younger age compared with group B (P=0.04). A statistically significant association was seen between polysomy 8 status and hepatosplenomegaly, fever, and lymph node infiltration (P=0.03, <0.001, and 0.05, respectively) but insignificant difference regarding the presence of skin or central nervous system infiltration (P>0.05). The presence of hepatosplenomegaly, skin infiltration, lymph node infiltration, and French–American–British subtype was shown to have a significant impact on patient outcome (P=0.05, 0.03, 0.01, and 0.04, respectively). Patients with skin infiltration, CD34 expression, HLA-DR expression, high/intermediate cytogenetic risk, and presence of polysomy 8 had significantly shorter overall survival.

Conclusion and recommendations

From the current study we conclude that polysomy 8 occurs in 27.8% of de-novo AML cases; 35% of these cases showed tetrasomy of chromosome 8. Polysomy of chromosome 8 was associated with shortened overall survival. Further studies with a larger number of patients are recommended for proper assessment of polysomy 8, especially tetrasomy 8, among Egyptian patients with AML.

Keywords: acute myeloid leukemia, fluorescence in-situ hybridization, polysomy 8


How to cite this article:
El Kerdany TA, Kayed HF, Saad AA, El-Dine El-Gaafary SS, Moustafa NN. Polysomy 8 in Egyptian patients with de-novo acute myeloid leukemia. Egypt J Haematol 2012;37:213-20

How to cite this URL:
El Kerdany TA, Kayed HF, Saad AA, El-Dine El-Gaafary SS, Moustafa NN. Polysomy 8 in Egyptian patients with de-novo acute myeloid leukemia. Egypt J Haematol [serial online] 2012 [cited 2020 Mar 28];37:213-20. Available from: http://www.ehj.eg.net/text.asp?2012/37/4/213/134967


  Introduction Top


Acute myeloid leukemia (AML) is an aggressive hematological neoplasia characterized by accumulation of myeloid precursor cells in bone marrow (BM) and in peripheral blood (PB) 1.

Over the past three decades, there have been marked advances in deciphering the cytogenetic and molecular lesions underlying the pathogenesis of AML. Cytogenetics is the most powerful single prognostic factor for outcome in AML and the most useful guide available for stratification and planning after remission treatment in this disease 2,3.

An additional chromosome 8 is the most common numerical abnormality in AML. Trisomy 8 (+8) occurs either at diagnosis as an apparently primary event or during the progression of the disease as a secondary chromosomal change 4. Patients with AML and +8 are generally included in the intermediate cytogenetic group in treatment protocols 5.

Tetrasomy, pentasomy, and hexasomy of chromosome 8 (polysomy 8) are relatively rare compared with +8 6,7. Polysomy 8 presents either as a sole anomaly or as part of complex defects. It may occur as an additional change or as an unrelated abnormal clone 8.

Two nonexclusive hypotheses have been proposed describing the mechanisms of polysomy 8 formation. In most cases of tetrasomy 8, the tetrasomic clone was observed in the presence of cells with +8 detected by conventional cytogenetics/or fluorescence in-situ hybridization (FISH), suggesting a stepwise evolution from disomy to tetrasomy through an intermediate stage of +8 by two consecutive mitotic nondisjunctions. Alternatively, tetrasomy may also occur as a result of the simultaneous nondisjunction of both homologues during a single cell division, and the trisomic clone could arise from the subsequent loss of one chromosome 8. Similar hypotheses may account for the admixture of cells with 3, 4, 5, or 6 chromosomes 8 in cases of pentasomy and hexasomy 8 9–12.

Although polysomy 8 appears to adversely influence outcome, little is known about the prognostic significance of polysomy 8 in patients with AML and whether the presence of additional defects has a prognostic impact in these patients. Indeed a number of patients have been reported as isolated cases or as part of a larger series where they have been analyzed together with patients with trisomy 8 alone or other chromosomal abnormalities, thus making it difficult to draw clear-cut conclusions 8.

The aim of the present work was to study the numerical aberrations of chromosome 8 in AML and to clarify its role as a prognostic marker.


  Patients and methods Top


Patients

The present study was carried out on newly diagnosed 76 adult patients with AML. They were attending the adult Hematology Department of Ain Shams University Hospitals. Their ages ranged from 16 to 68 years with a mean age of 39.7±13.6 years. There were 40 male and 36 female patients with a male-to-female ratio of 1.1 : 1. The least follow-up period was 1 year for surviving patients. The study protocol was approved by Ain Shams Medical Research Ethical Committee.

All the studied patients were subjected to full history taking and a thorough clinical examination laying stress on the presence of fever, hepatosplenomegaly (HSM), skin infiltration, central nervous system infiltration and lymphadenopathy.

Laboratory data were collected from patient files. They included complete blood count, examination of Leishman-stained PB and BM smears, myeloperoxidase stain, serum lactate dehydrogenase (LDH) and immunophenotyping of BM aspirates or PB samples.

For all studied patients conventional cytogenetics using G-banding and FISH using a fluorophore-labeled centromeric probe for chromosome 8 was studied.

All patients, except those with M3, received the standard induction protocol that consisted of cytarabine (Ara-C) and anthracycline (Daunorubicin vs. Idarubicin) administered as 100 mg/m2 of Ara-C daily in the form of continuous intravenous infusion for 7 days plus 45 mg/m2 of Daunorubicin or 12 mg/m2 of Idarubicin (in case of any cardiac problem and in patients over 60 years) given intravenously daily for 3 days, a combination called 3+7. This was followed by consolidation using 1–2 g/m2 high-dose Ara-C every 12 h for six to eight doses for one to two cycles followed by autologous or allogenic hematopoietic stem cell transplantation depending on the patient’s risk 13,14.

With regard to patients with M3 the standard induction protocol is the combination of all-trans retinoic acid at a dose of 45 mg/m2/day administered orally as a single dose plus anthracyclin (Idarubicin) at a dose of 12 mg/m2 administered intravenously on days 2, 4, 6, and 8 of a 28-day cycle 15.


  Methods Top


Sampling

A volume of 1 ml of BM aspirate (or PB in case of an insufficient BM sample) was collected in a sterile preservative-free lithium heparin-coated vacutainer tube for cytogenetic analysis.

Conventional cytogenetics and fluorescence in-situ hybridization studies

Metaphase cells from BM aspirate samples were cultured for 24 and 48 h and the slides were prepared and G-banded by conventional methods according to Schoch et al. 16.

FISH was performed using a fluorophore-labeled centromeric probe (Kreatech, Amsterdam, the Netherlands) for detection of chromosome 8 centromeres. This technique is based on denaturation of target DNA followed by hybridization to a complementary single-stranded nucleic acid sequence (fluorochrome-labeled) probe. Reaction conditions were adjusted so that hybridization occurs only between the probe and target DNA sequence of high homology. Target DNA is made visible by counterstaining with a DNA-specific fluorescent dye.

Probe interpretation

For each sample, at least 200 interphase cells were scanned under the chromoscan image analysis (CytoVision 2.7; Santa Clara, California, USA). The scanned cells were then captured using oil immersion objective and an appropriate filter set for the detection of chromosome 8 centromere. Only interphases with clear signals and no overlapping were analyzed. Normally, cells show two green signals corresponding to normal chromosome 8 diploidy, whereas three, four, and five green signals correspond to trisomy, tetrasomy, and pentasomy of chromosome 8, respectively. The cutoff level for positivity was 1.0%.

Statistical analysis

Analysis of data was carried out using an IBM computer with SPSS (Statistical program for Social Science version 15) (SPSS Inc., Chicago, Illinois, USA) as follows: description of quantitative variables as mean, SD and range and description of qualitative variables as number and percentage. The χ2-test and the Fisher exact test (for tables containing values <5) were used to compare groups regarding polysomy 8 status and patient outcome. Student’s t-test and the Mann–Whitney test (for nonparametric data) were used to assess the statistical significance of the difference according to polysomy 8 status and patient outcome.

Overall survival (OS) was determined using Kaplan–Meier curves; the log-rank test was used to calculate P values. Variables significantly related to OS were then included in the multivariate Cox proportional hazard regression model. Probability or P value less than or equal to 0.05 was considered statistically significant. OS was calculated as the time between diagnosis and the day of last follow-up or death.


  Results Top


The results of this study are summarized in [Table 1], [Table 2] and [Table 3] and [Figure 1], [Figure 2] and [Figure 3]. Our study was carried out on 76 cases of adult patients with AML; 40 of them were male and 36 were female with a male-to-female ratio of 1.1 : 1. Their ages ranged from 16 to 68 years with a mean of 39.7±13.6 years.
Figure 1: Kaplan–Meier curves illustrating overall survival of the patients according to: (a) skin manifestation; (b) CD34 expression; (c) HLA-DR expression; (d) cytogenetic risk; (e) presence of polysomy 8.

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Figure 2: Conventional cytogenetic analysis by G-banding showing: (a) male karyotype with +8 and t(5;7); (b) male karyotype with trisomy 3 and tetrasomy 8.

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Figure 3: Interphase fluorescent in-situ hybridization analysis showing (a) trisomy of chromosome 8; (b) tetrasomy of chromosome 8.

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Table 1: Relationship between patients characteristics and the presence of polysomy 8

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Table 2 Association between clinical and laboratory data and response to therapy

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Table 3 Kaplan–Meier overall survival estimates

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Conventional karyotyping and fluorescence in-situ hybridization analysis

Out of the 76 cases, 56 (73.7%) showed a successful mitosis. Among them, 20 (35.7%) were in the favorable cytogenetic risk group [t(8;21), inv16 or t(15;17)], 22 (39.3%) were in the intermediate-risk group (normal karyotype and +8), and 14 (25%) were in the high-risk group [complex karyotype, monosomy 7, monosomy 5, trisomy 11, or t(9;22)].

Metaphase and interphase FISH for detection of polysomy 8 was successfully performed on 72 samples, and +8 was found in 20 (27.8%) cases.

Tetrasomy of chromosome 8 was present in association with +8 in seven patients; their ages ranged from 21 to 36 years with a mean age of 24.3 years; four were male and three were female. All cases were associated with HSM. The mean hemoglobin level was 6.7 g/dl, total leukocytic count (TLC) was 30.7×109/l, and platelet count was 64×109/l. The mean PB blast percentage, BM blast percentage, and the absolute PB blast count were 49.3, 83% and 13.5×109/l, respectively. The mean serum LDH was 1259.6 IU/l. All cases had a mean OS of 5.3 months. A minor clone of pentasomy of chromosome 8 was revealed in association with tetrasomy and +8 clones in only one patient.

We divided the studied patients into two groups: group A comprised patients associated with polysomy 8 (20 cases; 27.8%) and group B comprised patients without polysomy 8 (52 cases; 72.2%).

Association between the presence of polysomy 8 and patients’ clinical and laboratory data is shown in [Table 1].

Group A cases showed statistically significant younger age compared with group B (P=0.04), with no significant difference between the two groups regarding sex (P=0.7).

Polysomy status was significantly associated with HSM, fever, and lymph node (LN) infiltration (P=0.03, <0.001, and 0.05, respectively) but not with the presence of skin or central nervous system infiltration (P>0.05).

Statistically insignificant association was seen between polysomy 8 status and hemoglobin level, TLC, platelet count, blast percentage (both in BM and PB), and LDH levels (P>0.05).

The median absolute PB blast count was significantly higher in group A cases (P=0.04). This was not the case with BM blast percentage in which the trend toward higher values did not reach statistical significance (P=0.07).

To evaluate the prognostic impact of French–American–British (FAB) subtypes, we divided our patients with AML into three groups: group I (M0–M2), which included 40 (55.6%) cases; group II (M3), which included 16 (22.2%) cases; and group III (M4–M5), which included 16 (22.2%) cases. Group A was not equally distributed among the different FAB subtypes. The frequency of polysomy 8 in relation to FAB subtype was ranked as follows: M3>M0–M2>M4–M5. However, no significant association was found between polysomy 8 status and a specific FAB subtype (P=0.2).

No significant association could be seen between polysomy 8 status and CD34 or HLA-DR expression (P>0.05). Twenty-eight cases (38.9%) revealed aberrant lymphoid marker expression. Among these 28 cases, 15 (53.6%) aberrantly expressed CD7, nine (32.1%) expressed CD19, two (7.1%) expressed CD2, and two expressed CD5.

Impact of the different studied parameters on response to therapy and overall survival

As regards clinical course and outcome, 56 out of the 76 patients (73.7%) showed good response to therapy and achieved complete remission, whereas the remaining 20 (26.3%) showed poor response to therapy [Table 2] and [Table 3].

The presence of HSM, skin infiltration, LN infiltration, and FAB subtype had significant impact on patient’s outcome (P=0.05, 0.03, 0.01, and 0.04, respectively).

OS was estimated from the time of diagnosis to the date of death or last visit.

Patients with skin infiltration, CD34 expression, HLA-DR expression, high/intermediate cytogenetic risk, and presence of polysomy 8 had significantly shorter OS. When these variables were included in Cox regression analysis, the presence of skin infiltration, cytogenetic risk, and polysomy 8 status proved to be the significantly influencing factors (95% confidence interval=3.573–53.034, 1.06–3.092, 1.369–7.019; P=0.001, 0.03, and 0.007, respectively).


  Discussion Top


In this study, 76 newly diagnosed adult patients with AML were studied for the presence of polysomy 8 using conventional karyotyping and FISH analysis. Follow-up of patients was carried out for not less than 1 year for surviving patients to determine outcome.

In the current study, cytogenetic analysis was successfully performed for 56 patients (73.7%). This is in agreement with the study by Klaus et al. 17 who reported that failed cytogenetics in patients with AML because of technical/biological parameters varies between 30 and 60%.

Metaphase and interphase FISH for detection of polysomy 8 was successfully performed on 72 samples and revealed polysomy of chromosome 8 in 27.8% of the cases. This is lower than that found in studies conducted by Jaff et al. 6 and Schaich et al. 7, who studied 131and 154 patients, respectively, and reported an incidence of 69 and 48%, respectively.

In the current study, tetrasomy 8 was presented in only seven cases. Moreover, tetrasomy of chromosome 8 was always found with a major clone of +8. This is in agreement with the results of the study by Kameoka et al. 11, Yan et al. 12, and Tsirigotis et al. 18, who implicate that tetrasomy 8 is closely related to +8 and it usually occurs by two consecutive events on nondisjunction: the first one produces +8 and the second one evolves the tetrasomy 8 clone.

Although Paulsson and Johansson 5 found increasing frequency of +8 by age in patients with AML, in our study, we found that cases with polysomy 8 showed a tendency toward younger mean age (33.6). Interestingly, patients with tetrasomy 8 showed a much younger mean age (24.3). This could be attributed to the fact that the mean age of the studied patients was 39.7 years, which is younger than the mean age in the previously mentioned study.

In contrast to Jaff et al. 6, a significant association between polysomy 8 and fever, HSM, and absence of LN infiltration was revealed in the current study.

Regarding complete blood count and BM data, we found significant association between polysomy 8 and higher absolute blast count and a trend toward higher BM blast percentage. In addition, patients with tetrasomy 8 had higher TLC, PB, and BM blast percentage and absolute blast count than did patients with +8 alone. Lei et al. 19 found a significant association between the presence of polysomy 8 and PB blast percentage. Furthermore, Jaff et al. 6 reported a high white blood cell (WBC) count association with polysomy 8. In contrast, Wolman et al. 20 and Lei et al. 19 found that polysomy 8 is more liable to occur with lower WBC count.

Regarding the FAB subtypes, the higher incidence of polysomy 8 was among the M0–M2 group of patients. Moreover, four out of seven tetrasomy 8 patients were categorized as FAB M0–M2. However, Tsirigotis et al. 18; Beyer et al. 8; and Yan et al. 12 reported that the group harboring the larger +8 had the M4/M5 subtype. Besides, Jaff et al. 6 and Udayakumar et al. 21 claimed that tetrasomy 8 involves the second rank in M2 after M5. This might be explained by the limited number of cases with M4/M5 phenotype included in our study.

The prognosis of AML depends on several factors such as age, initial WBC count, FAB subtype, karyotype, and immunophenotype. Among them, cytogenetics is the most important prognostic variable and is a major stratification tool after remission therapy 22.

In the current study, the mean OS of the polysomy 8-harboring group (7.5 months) was less than that of the polysomy 8-negative group (15.9 months). Furthermore, patients with tetrasomy 8 showed the shortest survival time (5.3 months). This is in accordance with the results of studies conducted by Jaff et al. 6 and Beyer et al. 8 reporting poor OS for patients with polysomy 8.

The unfavorable impact of polysomy 8 on survival has been a subject of many debates and provides many suggestions of the pathogenesis of AML in polysomy 8-harboring groups. Kameoka et al. 11; Virtaneva et al. 23; and Yan et al. 12 reported that the presence of extrachromosome 8 leads to duplication of certain oncogenes and proto-oncogenes on the short or long arm of chromosome 8, including c-myc, c-mos, RUNX1T1, and others. Jaff et al. 6 suggested that the leukemogenic process is probably because of altered expression of apoptosis-regulating genes, whereas our work supports the aggressive nature of polysomy 8 in patients with AML. However, the exact pathogenic mechanism of polysomy 8 requires further investigation.

Skin infiltration, CD34 and HLA-DR expression and cytogenetic risk stratification significantly affected the OS. This is in accordance with the studies by Weinberg et al. 24, Trost et al. 25, and Farag et al. 26.

From the current study we conclude that polysomy 8 occurred in 27.8% of de-novo AML cases. Tetrasomy of chromosome 8 occurred in 35% of +8 cases. Polysomy of chromosome 8 showed significant associations with younger age, presence of fever, HSM, LN infiltration, and high absolute blast count, as well as with shortened OS. Further studies including a larger number of patients are recommended for proper assessment of polysomy 8, especially tetrasomy 8, among Egyptian patients. These studies should involve different age groups and different immunophenotypes to better define the prognostic impact of polysomy 8 in acute leukemia, notably AML.[26]

 
  References Top

1.Hütter G, Letsch A, Nowak D, Poland J, Sinha P, Thiel E, Hofmann W. High correlation of the proteome patterns in bone marrow and peripheral blood blast cells in patients with acute myeloid leukemia. J Transl Med. 2009;7:7  Back to cited text no. 1
    
2.Grimwade D, Hills RK. Independent prognostic factors for AML outcome. Hematology. 2009;385:385–395  Back to cited text no. 2
    
3.Cervera J, Montesinos P, Hernández-Rivas J, Calasanz M, Aventín A, Ferro M, et al. Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Haematologica. 2010;95:424–431  Back to cited text no. 3
    
4.Batanian JR, Ma E, Huang Y, Gadre B. Co-existence of alternative forms of 8q gain in cytogenetics clones of three patients with acute myeloid leukemia, pointing to 8q22~8qter as a region of biologic significance. Cancer Genet Cytogenet. 2001;126:20–25  Back to cited text no. 4
    
5.Paulsson K, Johansson B. Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes. Pathol Biol. 2007;55:37–48  Back to cited text no. 5
    
6.Jaff N, Chelghoum Y, Elhamri M, Tigaud I, Michallet M, Thomas X. Trisomy 8 as sole anomaly or with other clonal aberrations in acute myeloid leukemia: impact on clinical presentation and outcome. Leuk Res. 2007;31:67–73  Back to cited text no. 6
    
7.Schaich M, Schlenk RF, Al-Ali HK, Döhner H, Ganser A, Heil G, et al. Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. Haematologica. 2007;92:763–770  Back to cited text no. 7
    
8.Beyer V, Mühlematter D, Parlier V, Cabrol C, Bougeon-Mamin S, Solenthaler M, et al. Polysomy 8 defines a clinico-cytogenetic entity representing a subset of myeloid hematologic malignancies associated with a poor prognosis: report on a cohort of 12 patients and review of 105 published cases. Cancer Genet Cytogenet. 2005;160:97–119  Back to cited text no. 8
    
9.Aktas D, Tuncbilek E, Cetin M, Hicsonmez G. Tetrasomy 8 as a primary chromosomal abnormality in a child with acute megakaryoblastic leukemia: a case report and review of the literature. Cancer Genet Cytogenet. 2001;126:166–168  Back to cited text no. 9
    
10.Athanasiadou A, Saloum R, Gaitatzi M, Anagnostopoulos A, Fassas A. Isolated pentasomy of chromosome 8 in erythroleukemia. Leuk Lymphoma. 2001;42:1409–1412  Back to cited text no. 10
    
11.Kameoka J, Funato T, Obara Y, Kadowaki I, Yokoyama H, Kimura T, et al. Clonal evolution from trisomy 8 into tetrasomy 8 associated with the development of acute myeloid leukemia from myelodysplastic syndrome. Cancer Genet Cytogenet. 2001;124:106–108  Back to cited text no. 11
    
12.Yan J, Marceau D, Drouin R. Tetrasomy 8 is associated with a major cellular proliferative advantage and a poor prognosis: two cases of myeloid hematologic disorders and review of literature. Cancer Genet Cyotgenet. 2001;125:14–20  Back to cited text no. 12
    
13.Bishop J. The treatment of adult acute myeloid leukemia. Semin Oncol. 1997;24:57–69  Back to cited text no. 13
    
14.Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: review article recommendation from an international expert panel, on behalf of the European Leukemia Net. Blood. 2010;115:453–474  Back to cited text no. 14
    
15.Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988;72:567–572  Back to cited text no. 15
    
16.Schoch C, Schnittger S, Klaus M, et al. AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood. 2003;102:2395–2402  Back to cited text no. 16
    
17.Klaus M, Haferlach T, Schnittger S, Kern W, Hiddemann W, Schoch C. Cytogenetic profile in de novo acute myeloid leukemia with FAB subtypes M0, M1, and M2: a study based on 652 cases analyzed with morphology, cytogenetics, and fluorescence in situ hybridization. Cancer Genet Cytogenet. 2004;155:47–56  Back to cited text no. 17
    
18.Tsirigotis P, Papageorgiou S, Abatzis D, Athanatou S, Girkas C, Pappa V, et al. Acute myelogenous leukemia with tetrasomy 8 is a disease with a poor prognosis. Cancer Genet Cytogenet. 2005;161:78–81  Back to cited text no. 18
    
19.Tian L, Liu LB, Wang XB, Xiao J, Zou P. Impact of trisomy 8 on cytobiological and clinical features of acute myelomonocytic and monocytic leukemia. J Exp Hematol. 2005;13:364–368  Back to cited text no. 19
    
20.Wolman SR, Gundacker H, Appelbaum FR, Slovak M. Impact of trisomy 8 (+8) on clinical presentation, treatment response, and survival in acute myeloid leukemia: a Southwest Oncology Group study. Blood. 2002;100:78–81  Back to cited text no. 20
    
21.Udayakumar M, Pathare A, Al-Kindi S, Khan H, Rehmen J, Zia F, et al. Cytogenetic, morphological, and immunophenotypic patterns in Omani patients with de novo acute myeloid leukemia. Cancer Genet Cytogenet. 2007;177:89–94  Back to cited text no. 21
    
22.Small D. Targeting FLT3 for treatment of leukemia. Semin Hematol. 2008;45:S17–S21  Back to cited text no. 22
    
23.Virtaneva K, Wright FA, Tanner SM, Yuan B, Lemon WJ, Caligiuri MA, et al. Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Natl Acad Sci USA. 2001;98:1124–1129  Back to cited text no. 23
    
24.Weinberg O, Seetharam M, Ren L, Seo K, Ma L, Gotlib J, et al. Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system. Blood. 2009;113:1906–1908  Back to cited text no. 24
    
25.Trost D, Hildebrandt B, Beier M, Müller N, Germing U, Royer-Pokora B. Molecular cytogenetic profiling of complex karyotypes in primary myelodysplastic syndromes and acute myeloid leukemia. Cancer Genet Cytogenet. 2006;165:51–63  Back to cited text no. 25
    
26.Farag SS, Archer KJ, Mrózek K, Ruppert AS, Caroll AJ, Vardiman JW, et al. Pretreatment cytogenetics adds to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood. 2006;108:63–73  Back to cited text no. 26
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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