Detection of the CBFB/MYH11 fusion gene in de novo acute myeloid leukemia (AML): A single-institution study of 224 Japanese AML patients

2007 ◽  
Vol 31 (4) ◽  
pp. 471-476 ◽  
Author(s):  
Fumihiko Monma ◽  
Kazuhiro Nishii ◽  
Junko Shiga ◽  
Haruka Sugahara ◽  
Felipe Lorenzo ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Fusion Gene ◽  
Single Institution ◽  
Acute Myeloid

Coexpression of NUP98/TOP1 and TOP1/NUP98 in de novo Acute Myeloid Leukemia with t(11;20)(p15;q12) and t(2;5)(q33;q31)

2016 ◽  
Vol 150 (3-4) ◽  
pp. 287-292
Author(s):  
Katsuya Yamamoto ◽  
Yosuke Minami ◽  
Kimikazu Yakushijin ◽  
Yu Mizutani ◽  
Yumiko Inui ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Fusion Gene ◽  
Fusion Transcript ◽  
Fish Analysis ◽  
Balanced Translocation ◽  
Cytogenetic Aberration ◽  
De Novo Aml ◽  
Acute Myeloid

The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.

scholarly journals Cytogenetic profile of de novo acute myeloid leukemia: a study based on 1432 patients in a single institution of China

Leukemia ◽  
2009 ◽  
Vol 23 (10) ◽  
pp. 1801-1806 ◽  
Author(s):  
Y Cheng ◽  
Y Wang ◽  
H Wang ◽  
Z Chen ◽  
J Lou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Single Institution ◽  
Cytogenetic Profile ◽  
Acute Myeloid

Acute Myeloid Leukemia (AML) with t(6;9)(p23;q34) Defines a Very Poor Risk Leukemia Subgroup with Distinguishing Clinicopathological Features: A United States (US) Cytogenetics Intergroup Study of 62 AML and MDS Cases.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 567-567
Author(s):  
Marilyn L. Slovak ◽  
Clara D. Bloomfield ◽  
Holly Gundacker ◽  
Gordon Dewald ◽  
Frederick R. Appelbaum ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Fusion Gene ◽  
Young Patients ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Published Data ◽  
Pediatric Aml ◽  
Acute Myeloid

Abstract The t(6;9)(p23;q34) translocation, which results in the formation of a chimeric fusion gene DEK/CAN on the der(6) chromosome, is a rare recurring cytogenetic aberration reported in patients (pts) with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Because the abnormality is an infrequent finding in AML with most reports describing 2 to 8 cases, the US Intergroup Cytogenetics Consortium investigated the frequency and clinical, pathologic and cytogenetic characteristics of t(6;9) leukemia among pts registered to 19 different treatment protocols. Among 6567 pts with evaluable karyotypes, 62 (0.9%) had t(6;9): 30 on pediatric trials (mean 12 yrs; 15/15 male/female) and 32 on adult trials (mean 38 yrs; 21/11 male/female), compared to the mean age of 8 yrs for pts on pediatric AML/MDS trials and 54 yrs for pts on adult AML/MDS trials. Three cases (5%) showed a complex (3- or 4-way) variant translocation and only 7 (11%) of the 62 pts showed secondary aberrations: 3 (10%) of 30 pediatric cases and 4 (13%) of 32 of the adult cases. The majority of t(6;9) cases were classified as FAB-M2 (34%), M4 (31%) or M1 (19%). Although the immunophenotyping (N=7) and morphology data (N=17) were limited, increased basophilia and Auer rods were observed and the blasts showed CD13, CD15, and CD33 expression, in agreement with a previously reported preliminary study (Am J Clin Pathol107:430–437,1997). Four pts (1 pediatric and 3 adults) had MDS. Among the remaining 58 pts, 25 (78%) adults had previously untreated AML (16 de novo, 2 secondary, and 7 unknown secondary/de novo status) while all 29 pediatric AML patients had de novo AML. For the 54 patients with previously untreated AML, complete remission rates were slightly higher, but not statistically significantly (p=.20) in children (69%), when compared to adults (52%). Disease-free survival (DFS) (combined median 8.8 mo, 95% CI, 5.1–13.7) and overall survival (OS) (combined median 11.9 mo, 95% CI, 10.0–14.3) were poor regardless of age, a finding in distinct contrast to the t(8:21) favorable risk group also commonly observed in M2/M4 AML. Kaplan-Meier estimates of 3-yr survival were 25% for pediatric cases and 9% for adults. Analysis of stem cell transplantation (SCT) was inconclusive due to the small number of transplanted patients (N=15), but suggested that allogeneic SCT might be associated with better OS than no SCT (hazard ratio [HR] 0.39 after SCT, 95% CI 0.14 – 1.11), while autologous SCT might not (HR 1.49, 95% CI 0.57–3.85). Based on this study of t(6;9), largest to date and previously published data, AML with t(6;9) leukemia is a distinct AML subgroup with distinguishing clinicopathological features including poor outcome in relatively young patients, not explained by other known poor prognostic factors that warrants novel therapeutic strategies. Similar to other recurring cytogenetic abnormality subtypes of de novo acute myeloid leukemia of the WHO classification, t(6;9) may warrant a specific leukemia disease subtype.

scholarly journals First case report of a NUP98-PMX1 rearrangement in de novo acute myeloid leukemia and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Weijia Fu ◽  
Aijie Huang ◽  
Hui Cheng ◽  
Yanrong Luo ◽  
Lei Gao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Fusion Gene ◽  
High Dose ◽  
Rt Pcr ◽  
Hematopoietic Stem ◽  
First Report ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Background The nucleoporin 98 (NUP98)-paired related homeobox 1 (PMX1) fusion gene, which results from t(1;11)(q23;p15), is rare in patients with acute myeloid leukemia (AML). Currently, only two cases of chronic myeloid leukemia in the accelerated phase or blast crisis and three cases of therapy-related AML have been reported. Here, we first report a patient with de novo AML carrying the NUP98-PMX1 fusion gene. Case presentation A 49-year-old man diagnosed with AML presented the karyotype 46,XY,t(1;11)(q23;p15)[20] in bone marrow (BM) cells. Fluorescence in situ hybridization analysis using dual-color break-apart probes showed the typical signal pattern. Reverse transcription-polymerase chain reaction (RT-PCR) analysis suggested the presence of the NUP98-PMX1 fusion transcript. The patient received idarubicin and cytarabine as induction chemotherapy. After 3 weeks, the BM aspirate showed complete remission, and the RT-PCR result for the NUP98-PMX1 fusion gene was negative. Subsequently, the patient received three cycles of high-dose Ara-c as consolidation chemotherapy, after which he underwent partially matched (human leukocyte antigen–DP locus mismatch) unrelated allogeneic hematopoietic stem cell transplantation (HSCT). The follow-up period ended on September 30, 2020 (6 months after HSCT), and the patient exhibited no recurrence or transplantation-related complications. Conclusion This is the first report of a patient with de novo AML carrying the NUP98-PMX1 fusion gene. The reported case may contribute to a more comprehensive profile of the NUP98-PMX1 rearrangement, but mechanistic studies are warranted to fully understand the role of this fusion gene in leukemia pathogenesis.

scholarly journals Mutation of NPM1 and FLT3 Genes in Acute Myeloid Leukemia and Their Association with Clinical and Immunophenotypic Features

2013 ◽  
Vol 35 ◽  
pp. 581-588 ◽  
Author(s):  
Pradeep Singh Chauhan ◽  
Rakhshan Ihsan ◽  
L. C. Singh ◽  
Dipendra Kumar Gupta ◽  
Vishakha Mittal ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Fusion Gene ◽  
Genetic Alterations ◽  
Prognostic Indicators ◽  
White Blood Count ◽  
Npm1 Mutation ◽  
De Novo Aml ◽  
Acute Myeloid

Background.Mutations in NPM1 and FLT3 genes represent the most frequent genetic alterations and important diagnostic and prognostic indicators in patients with acute myeloid leukemia (AML).Objective.We investigated the prevalence and clinical characteristics of NPM1 and FLT3 mutations in 161 patients of de novo AML including adults and children.Results.NPM1 mutation was found in 21% and FLT3 mutation in 25% of the AML patients. Thirteen (8%) samples were positive for both NPM1 and FLT3/ITD mutations. Adult patients had significantly higher frequency of NPM1 mutation than children (25.8% versus 8.8%;P=0.02). Further, NPM1 mutation was found to be more frequent in patients above 45 years of age (P=0.02). NPM1 mutation was significantly associated with higher platelet count (P=0.05) and absence of hepatosplenomegaly (P=0.01), while FLT3/ITD mutation was associated with higher white blood count (P=0.01). Immunophenotypically, NPM1 mutation was associated with the lack of CD34 (P<0.001) and HLD-DR expression (P<0.001), while FLT3/ITD mutation was positively associated with the expression of CD7 (P=0.04). No correlation was found between NPM1 mutation and fusion gene. Interestingly, FLT3/ITD mutation was found to be inversely associated with AML/ETO fusion gene (P=0.04).Conclusions.The results suggest that distinct clinical and immunophenotypic characteristics of NPM1 and FLT3/ITD mutations present further insight into the molecular mechanism of leukemogenesis.

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