Chromosomal Aberration for Diagnosis and Prognosis of Acute Myeloid Leukemia Iraqi Patients

Background: Acute myeloid leukemia (AML) is a hematopoietic disorder in which there are too many immature blood-forming cells accumulating in the bone marrow and interfering with the production of normal blood cells. It has long been recognized that AML is a clinically heterogeneous disease characterized by a multitude of chromosomal abnormalities and gene mutations, which translate to marked differences in responses and survival following chemotherapy. This study aimed to clarify the chromosomal aberrations in early diagnosed and relapsed cases of AML. Materials and methods: Chromosomal changes were studied in thirty Iraqi patient samples diagnosed with acute myeloid leukemia were divided into 9 newly diagnosed and 13 received chemotherapy who were incomplete remission and 8 relapsed subjects. Results: Analysis of all chromosomal aberrations showed complex karyotype for most cells of relapsed AML patients compared with newly diagnosed patients. Conclusions: Chromosomal abnormalities are linked to AML development and high complexity of karyotyping for relapsed group.

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The possible significance of trisomy 8 in acute myeloid leukemia

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20172464 ◽

2017 ◽

Vol 5 (6) ◽

pp. 2652 ◽

Cited By ~ 2

Author(s):

Salil N. Vaniawala ◽

Monika V. Patel ◽

Pratik D. Chavda ◽

Shivangi H. Zaveri ◽

Pankaj K. Gadhia

Keyword(s):

Acute Myeloid Leukemia ◽

Chromosomal Aberrations ◽

Myeloid Leukemia ◽

Chromosomal Abnormalities ◽

Prognostic Significance ◽

Chromosomal Translocation ◽

Banding Technique ◽

Trisomy 8 ◽

Increased Risk ◽

Acute Myeloid

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder that results from a block in the differentiation of haematopoietic progenitor cells along with uncontrolled proliferation. Trisomy 8 is the most common recurring numerical chromosomal aberrations in acute myeloid leukemia (AML). It occurs either as a sole anomaly or together with other additional chromosomal aberrations. The prognostic significance of trisomy 8 in presence of other additional chromosomal abnormality depends on clonal cytogenetic changes. The patients with trisomy 8 had shorter survival with significantly increased risk with other chromosomal abnormality.Methods: Total 139 patients were screened between January 2016 to November 2016 who were suspected of AML cases. Bone marrow cultures were set up using conventional cytogenetic methods. Chromosomal preparation was made and subjected to GTG banding technique. Banded metaphases were analysed and karyotyped for further analysis.Results: Cytogenetic evaluation of karyotyped of 139 suspected AML patients showed 52 with t(8;21)(q22;q22), 36 with t(15;17)(q22;q12), and 11 with inv(16)(p13;q22). The rest 40 cases found with additional chromosomal abnormalities, of which 16 were sole trisomy 8 and 24 cases were found with other chromosomal abnormalities In addition, only one person found with t(8;21) and trisomy 8, while three person having t(15;17) with trisomy 8.Conclusions: AML is considered to be one of the most important cytogenetic prognostic determinants. Recurrent chromosomal translocation with trisomy 8 varying 1.9% for t(8;21) and 8.3% for t(15;17). In the present study trisomy 8 in AML with known favourable anomalies is very small. Therefore, it cannot be taken as a prognostic marker.

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Hematopoietic Stem Cell Transplantation (HSCT) Benefits the Survival of Acute Myeloid Leukemia (AML) Patients with IDH1, NRAS and DNMT3A Mutations

Blood ◽

10.1182/blood.v120.21.1981.1981 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1981-1981

Author(s):

Yang Xu ◽

Zhen Yang ◽

Hong Tian ◽

Huiying Qiu ◽

Aining Sun ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Myeloid Leukemia ◽

Gene Mutations ◽

Newly Diagnosed ◽

Hematopoietic Stem ◽

Acute Myeloid

Abstract Abstract 1981 Background: Gene mutations may serve as potential markers to extend the prognostic parameters in acute myeloid leukemia (AML) patients. In this study, we detected distribution of mutations in the nucleophosmin gene (NPM1), C-KIT, the fms-related tyrosine kinase 3 gene (FLT3), Isocitrate dehydrogenase gene 1 and 2 (IDH1, IDH2), the neuroblastoma RAS viral oncogene homolog (NRAS) and DNA methyltransferase 3A gene (DNMT3A) in 442 newly diagnosed AML patients (none-APL). Associations of gene mutations with clinical outcomes in these patients followed HSCT treatment or chemotherapy were further evaluated. Methods: Between February 2005 and December 2011, 442 newly diagnosed AML (none-APL) patients in our centre were retrospectively analyzed. There are 248 males and 194 females, and the median ages were 40 (16–60) years. 393 patients (88.9%) of patients were with single or normal karyotype and 49 patients (11.1%) were with complex abnormal karyotype. In addition to MICM examination, direct sequencing was employed to access the distribution of mutations in of FLT3-ITD (exon14), FLT3-TKD (exon 20), NPM1 (exon12), C-KIT (exon8, 17), IDH2 (exon 4), NRAS (exon1, 2), DNMT3A (exon23) of 445 AML patients. Complete remission (CR) was achieved in 258 patients (58.4%) followed the standard induction therapy, 128 patients received HSCT (Allo-HSCT: 121 vs. Auto-HSCT: 7) therapy after first remission or second remission while 258 patients received consolidation chemotherapy contained 4–6 cycles high dose Ara-C (HD-Ara-C). Overall survival (OS) and Event-free survival (EFS) were measured at last follow-up (censored), and Kaplan-Meier analysis was used to calculate the distribution of OS and EFS. Results: In 442 AML (None-APL) patients, 44 patients (9.7%) had C-KIT mutations, 97 patients (21.9%) had NPM1 mutations, 95 patients (21.5%) had FLT3-ITD mutations, 26 patients (5.9%) had FLT3-TKD mutations, 23 patients (5.2%) had IDH1 mutations, 48 patients (10.9%) had IDH2 mutations, 31 patients (7.0%) had DNMT3A mutations, and 40 patients (9.0%) had NRAS mutations. Using COX regression, we found that mutations in FLT3-ITD (HR:2.113; 95%CI: 1.1420 to 3.144),IDH1 (HR:3.023; 95%CI: 1.055 to 3.879), NRAS (HR:1.881; 95%CI: 1.021 to 2.945), and DNMT3A (HR: 2.394; 95%CI: 1.328 to 4.315) were independent unfavorable prognostic indicators of overall survival of AML patients. We further compared the outcomes of AML patients with such gene mutations followed different therapy (HSCT vs. HD Ara-C), and results shown that patients with mutations in IDH1, NRAS and DNMT3A received HSCT therapy had better survival. The median OS and EFS of patients with FLT3-ITD, IDH1, NRAS and DNMT3A in the two groups (HSCT vs. HD Ara-C) were as follows: IDH1 (OS: 35 months vs. 11 months, p=0.016; EFS: 34 months vs. 8 months, p=0.012), NRAS (OS: 27months vs. 8 months, p=0.008; EFS: 23 months vs. 4 months, p=0.049), DNMT3A (OS: 66 months vs. 19 months, p=0.008; EFS: 54 months vs. 13 months, p=0.002). Conclusions: Taken together, our data proved that mutant FLT3-ITD, IDH1, NRAS, and DNMT3A might serve as poor prognostic markers and hematopoietic stem cell transplantation as first-line treatment could favor the outcome of AML patients carrying IDH1, NRAS, and DNMT3A mutations. Disclosures: No relevant conflicts of interest to declare.

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Gene Mutations in Paired Initial Presentation and Relapse Samples From Acute Myeloid Leukemia Patients,

Blood ◽

10.1182/blood.v118.21.3592.3592 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3592-3592

Author(s):

Satoshi Wakita ◽

Hiroki Yamaguchi ◽

Yoshio Mitamura ◽

Fumiko Kosaka ◽

Takashi Shimada ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Chromosomal Aberrations ◽

Myeloid Leukemia ◽

De Novo ◽

Risk Group ◽

Gene Mutations ◽

Initial Presentation ◽

Paired Samples ◽

De Novo Aml ◽

Acute Myeloid

Abstract Abstract 3592 Introductions: Gene mutationswere found in acute myeloid leukemia (AML) and their importance has been noted. Flt3, NPM1 and CEBPA were detected in “intermediate cytogenetic risk” group, and are becoming possible to distinguish subsets of patients with different outcomes. Moreover, several groups have reported that these mutations would be useful for not only predictive markers, but also minimal residual disease (MRD) markers in AML. Several recent studiesprovided compelling evidence that mutations in epigenetics modifying genes contribute to AML pathogenesis. DNMT3a mutations were common (about 20% frequency) in de novo AML and associated with poor prognosis. Furthermore, mutations of IDH1/2 and TET2 that also seem to be collaborating on DNA methylation modifying are detected, too. To clarify the importance and dynamics of these mutations in clinical course, we examined Flt3, NPM1, CEBPA, DNMT3a and IDH1/2 gene mutations in paired samples at initial presentation and relapse of AML patients. Materials and Methods: We analyzed the samples from adultpatients with de novo AML diagnosed at Nippon Medical School Hospital from 2000 to 2010. Mutation analyses were performed for Flt3 ITD by PCR amplification, Flt3 TKD by PCR-RFLP, and NPM1, CEBPA, IDH1/2 and DNMT3a mutations by direct sequence. Results: The 31 AML patients were enrolled. In chromosomal analysis at initial presentation, 19 with normal karyotype (NK-) AML, 2 with trisomy8, 4 with 11q23 associated, 1 with monosomy7, 2 with complex karyotypes and 3 with non-specific aberrations were observed. 15 cases were comparable for paired samples at diagnosis and relapse. 13 of them (86.7%) showed additional chromosomal aberrations at relapse. Gene mutations were detected more frequently in cytogenetic intermediate risk group (83.3%) than poor risk group (0%). There were 11 patients with Flt3 ITD at initial presentation, but 3 of them had no detectable mutation at relapse. Flt3 TKD were found in 3 patients at initial presentation, but all of them were lost at relapse. Among 12 patients with NPM1 mutation at initial presentation, 3 of them lost their mutation at relapse. CEBPA mutation was detected in only one paired sample at diagnosis and relapse. DNMT3a mutations were detected in 8 patients both at initial presentation and relapse. IDH2 mutations were detected in two patients at initial presentation, but 1 of them was lost at relapse. In summary, of the 37 gene mutations at initial presentation, 10 gene mutations were lost at relapse, and only 1 acquired gene mutation was detected at relapse. Flt3 ITD, NPM1, DNMT3a and IDH2 mutations frequently coexisted with another mutation. Discussion: This study is the first report of consecutive analyses on the major gene mutations in AML. Newly acquired gene mutations at relapse are rare compared to frequent additional chromosomal aberrations at relapse. Flt3 ITD mutations at initial presentation were detected also at relapse. This finding indicates that Flt3 ITD are responsible for relapse and refractoriness. On the other hand, all 3 cases with Flt3 TKD lost the mutation at relapse, suggesting that Flt3 TKD mutation does not contribute to their relapse. Some of Flt3 ITD, Flt3 TKD and NPM1 mutations could not be detected at relapse, indicating that these mutations should be used carefully for MRD marker. DNMT3a mutations were detected both at diagnosis and relapse in all 8 cases. This finding suggests that DNMT3a mutations might be a useful MRD marker. Disclosures: No relevant conflicts of interest to declare.

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Acute Myeloid Leukemia With t(8;21)/RUNX1-RUNX1T1 demonstrate a High Number Of Secondary Genetic Lesions: Frequency and Impact On Clinical Outcome

Blood ◽

10.1182/blood.v122.21.2565.2565 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2565-2565

Author(s):

Maria Theresa Krauth ◽

Christiane Eder ◽

Tamara Alpermann ◽

Wolfgang Kern ◽

Claudia Haferlach ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Chromosomal Aberrations ◽

Myeloid Leukemia ◽

De Novo ◽

Chromosomal Abnormalities ◽

Trisomy 8 ◽

Employment Equity ◽

Equity Ownership ◽

De Novo Aml ◽

Acute Myeloid

Abstract Background Translocation t(8;21) with the resulting RUNX1-RUNX1T1 rearrangement is one of the most common chromosomal abnormalities in acute myeloid leukemia (AML). Although it is generally associated with a favourable prognosis, many additional genetic lesions may impact on outcome. Aim To assess the frequency and clinical impact of additional mutations and chromosomal aberrations in AML with t(8;21)/RUNX1-RUNX1T1. Methods We analyzed 139 patients (pts) who were referred to our laboratory for diagnosis of AML between 2005 and 2012 (65 females, 74 males; median age 53.3 years, range 18.6 - 83.8 years). All pts were proven to have t(8;21)/RUNX1-RUNX1T1 by a combination of chromosome banding analysis, fluorescence in situ hybridisation and RT-PCR. Analysis of mutations in ASXL1, FLT3-TKD, KIT (D816, exon8-11), NPM1, IDH1 and IDH2, KRAS, NRAS, CBL, and JAK2 as well as of MLL-PTD and FLT3-ITD was performed in all pts. Results 107/139 pts were classified according to FAB criteria (77.0%). 34/107 had AML M1 (31.8%) and 73/107 AML M2 (68.2%). 117/139 had de novo AML (84.2%), 22/139 had therapy-related AML (t-AML) (15.8%). 69/139 (49.6%) pts had at least one molecular alteration in addition to RUNX1-RUNX1T1, 23/69 (33.3%) had two or more additional mutations. Most common were mutations (mut) in KIT (23/139; 16.5%), followed by NRAS (18/139; 12.9%) and ASXL1 (16/139; 11.5%). FLT3-ITD and mutations in FLT3-TKD, CBL, and KRAS were found in 4.3% - 5.0% of all pts, whereas mutations in IDH2 and JAK2 were detectable in 3.6% and 2.9%, respectively. IDH1 mutations were found in only 0.7% (1/139). NPM1mut and MLL-PTD were mutually exclusive of RUNX1-RUNX1T1. FLT3-ITD as well as FLT3-TKD were exclusive of ASXL1 mutations. With exception of FLT3-ITD, which was only present in de novo AML, there was no difference in mutation frequencies between de novo AML and t-AML. 69.8% (97/139) pts had at least one chromosomal aberration in addition to t(8;21)(q22;q22). Most frequent was the loss of either X- or Y-chromosome (together 46.8%), followed by del(9q) (15.1%), and trisomy 8 (5.8%). FLT3-ITD, FLT3-TKD and trisomy 8 were found to be mutually exclusive. The number of secondary chromosomal aberrations did not differ significantly between pts with de novo AML and t-AML, showing only a trend towards higher frequency of -Y, del(9q), and trisomy 8 in pts with t-AML. Survival was calculated in pts who received intensive treatment (n=111/139, 79.9%; median follow-up 26.9 months; 2-year survival rate 73.4%). With exception of KITD816 mutation, which had a negative impact on overall survival in pts with de novo AML (2-year survival rate 64.2% vs. 82.3%, p=0.03), none of the other 13 mutations significantly influenced outcome, not even in case of 2 or more coexistent mutations. Also, no influence of additional chromosomal aberrations on survival was found. In selected cases (n=21/139), we compared dynamic changes in the patterns of genetic lesions at diagnosis and at relapse. In 14/21 (66.7%) pts the initial molecular mutation pattern changed at relapse. Mutations commonly gained at relapse were KIT mutations (6/21, 28.6%), followed by ASXL1 and IDH1R132 (each 2/21, 9.5%). FLT3-ITD, CBL, NRAS and JAK2 mutations emerged in 1/21 patients (4.8%) each. Loss of a mutation at relapse has been observed in KIT, ASXL1, and NRAS (each 2/21, 9.5%), as well as in KRAS, FLT3-ITD and FLT3-TKD (each 1/21, 4.8%). Concerning chromosomal alterations at relapse, 7/21 pts (33.3%) showed a change of their initial cytogenetic pattern, mostly shifting to a more complex karyotype (gain of chromosomal aberrations: 5/21, 23.8%; loss of chromosomal aberrations: 2/21, 9.5%). In all cases, t(8;21)(q22;q22)/RUNX1-RUNX1T1 remained stable at time of relapse. Conclusions 1) 50% of t(8;21)/RUNX1-RUNX1T1 positive pts had at least one additional molecular mutation and almost 70% showed additional chromosomal abnormalities. 2) KIT was the most frequent additional molecular mutation, followed by NRAS and ASXL1. 3) The only additional genetic marker with a significant adverse prognostic impact was KITD816 mutation. Disclosures: Krauth: MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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Genomic Abnormalities as Biomarkers and Therapeutic Targets in Acute Myeloid Leukemia

Cancers ◽

10.3390/cancers13205055 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5055

Author(s):

Sara Ribeiro ◽

Anna M. Eiring ◽

Jamshid S. Khorashad

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Chromosomal Abnormalities ◽

Therapeutic Targets ◽

Gene Mutations ◽

Functional Methods ◽

Stem And Progenitor Cells ◽

Comprehensive Picture ◽

Proper Diagnosis ◽

Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous malignancy characterized by the clonal expansion of myeloid stem and progenitor cells in the bone marrow, peripheral blood, and other tissues. AML results from the acquisition of gene mutations or chromosomal abnormalities that induce proliferation or block differentiation of hematopoietic progenitors. A combination of cytogenetic profiling and gene mutation analyses are essential for the proper diagnosis, classification, prognosis, and treatment of AML. In the present review, we provide a summary of genomic abnormalities in AML that have emerged as both markers of disease and therapeutic targets. We discuss the abnormalities of RARA, FLT3, BCL2, IDH1, and IDH2, their significance as therapeutic targets in AML, and how various mechanisms cause resistance to the currently FDA-approved inhibitors. We also discuss the limitations of current genomic approaches for producing a comprehensive picture of the activated signaling pathways at diagnosis or at relapse in AML patients, and how innovative technologies combining genomic and functional methods will improve the discovery of novel therapeutic targets in AML. The ultimate goal is to optimize a personalized medicine approach for AML patients and possibly those with other types of cancers.

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

Blood ◽

10.1182/blood-2011-03-343467 ◽

2011 ◽

Vol 118 (20) ◽

pp. 5583-5592 ◽

Cited By ~ 103

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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Decreased Incidence of Clonal Evolution to Myelodysplastic Syndrome/Acute Myeloid Leukemia with Monosomy 7 in Children with Aplastic Anemia Following Reduced Use of G-CSF.

Blood ◽

10.1182/blood.v110.11.1696.1696 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1696-1696

Author(s):

Yoshiyuki Takahashi ◽

Akira Ohara ◽

Ryoji Kobayashi ◽

Hiromasa Yabe ◽

Masahiro Tsuchida ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Cumulative Incidence ◽

Myeloid Leukemia ◽

Chromosomal Abnormalities ◽

Clonal Evolution ◽

Newly Diagnosed ◽

Trisomy 8 ◽

Monosomy 7 ◽

Secondary Mds ◽

Acute Myeloid

Abstract A serious complication of aplastic anemia (AA) is evolution to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In a previous nationwide study conducted between 1988 and 1992 in Japan, 11 of 67 patients treated with immunosuppressive therapy (IST) and G-CSF developed MDS/AML with monosomy 7, giving a cumulative incidence of 47±17% over 6 years. In the study, all but one of the patients who developed MDS/AML had received G-CSF for more than 12 months. Recently, a European survey confirmed our finding that a significantly higher hazard of MDS/AML is associated with the use of G-CSF in patients with AA after IST. Another recent study also showed that a high concentration of G-CSF favors expansion of preexisting monosomy 7 clones in vitro. Since 1993, we prospectively examined the relationship between the development of MDS/AML with monosomy 7 and the use of G-CSF in newly diagnosed AA patients. Here, we report a marked decrease in the incidence of secondary MDS/AML with monosomy 7 in our prospective study for AA. From 1993 to 2006, 387 newly diagnosed AA children who received antithymocyte globulin (ATG) and cyclosporine with or without G-CSF entered the two consecutive prospective studies. Cytogenetic data were available in 377 patients. Eleven of these 377 patients were then excluded from the study because of cytogenetic abnormalities at diagnosis, consisting of 5 somatic chromosomal defects and 6 clonal abnormalities including one monosomy 7 and three trisomy 8. The median age of the 366 evaluable patients was 9 years, ranging from 1 to 18 years. The median follow up period of the surviving patients was 60 months (range: 1 to 167 months). The cumulative durations of G-CSF therapy were as follows: 0 days (n=111), 1–30 days (n=66), 31–60 days (n=70), 61–90 days (n=43), 91–180 days (n=52), 181–365 days (n=17), over 366 days (n=4), and unknown (n=3). Twenty-one of the 369 analyzed patients developed clonal cytogenetic abnormalities between 6 and 62 months (median: 18 months) after the time of diagnosis, giving a cumulative incidence of 7.1 ± 1.5% at 6 years. Cytogenetic analysis revealed monosomy 7 (10 patients), trisomy 8 (6 patients), others (5 patients) at the time of clonal evolution. The cumulative incidence of MDS/AML with monosomy 7 was 3.0 ± 1.0% in patients who received IST and G-CSF. Chromosomal abnormalities strongly predicted the outcome. Five of the 10 patients with monosomy 7 died without SCT. The remaining 5 patients who received SCT are currently alive. All of the 11 patients with other chromosomal abnormalities are also alive either with SCT (n=3) and without SCT (n=8). Three of the 10 patients with monosomy 7 received G-CSF for longer than 12 months and all of them died but none of the 11 patients with other chromosomal abnormalities received G-CSF over 12 months. Notably, although only 4 of the 366 patients received G-CSF over 12 months, three of them developed MDS/AML with monosomy 7. We observed a drastic decrease in the cumulative incidence of MDS/AML with monosomy7 in AA patients treated with IST and G-CSF. The current study confirms the finding of our previous report, which suggested a close relationship between long-term use of G-CSF and secondary MDS/AML with monosomy 7 in AA patients.

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