Correction to: Dysplastic features seen in a patient with acute myeloid leukemia harboring the KMT2A-TET1 fusion gene

AbstractThis study aims to explore the effect of the ITI (interferon alpha-1b, thalidomide, and interleukin-2) regimen on the AML1-ETO fusion gene in patients with t(8;21) acute myeloid leukemia (AML) who were in hematologic remission but positive for the AML1-ETO fusion gene. From September 2014 to November 2020; 20 patients with AML (15 from The Affiliated Cancer Hospital of Zhengzhou University, 4 from The First Affiliated Hospital; and College of Clinical Medicine of Henan University of Science and Technology, and 1 from Anyang District Hospital) with hematological remission but AML1-ETO fusion gene positivity were treated with different doses of the ITI regimen to monitor changes in AML1-ETO fusion gene levels. Twenty patients were treated with a routine dose of the ITI regimen, including 13 males and 7 females. The median patient age was 38 (14–70 years). The fusion gene was negative in 10 patients after 1 (0.5 ~ 8.6) month, significantly decreased in 4 patients after 2.8 (1 ~ 6) months, increased in 4 patients, and unchanged in 2 patients. The 4 patients with elevated levels of the fusion gene were treated with an increased dose of the ITI regimen, and all four patients became negative, for a total effective rate of 90%. The ITI regimen reduces AML1-ETO fusion gene levels in patients with AML who are in hematologic remission but are fusion gene–positive. Improvement was observed in patients’ response to a higher dose administration, and patients tolerated the treatment well.

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The specific distribution pattern of IKZF1 mutation in acute myeloid leukemia

Journal of Hematology & Oncology ◽

10.1186/s13045-020-00972-5 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Xiang Zhang ◽

Xuewu Zhang ◽

Xia Li ◽

Yunfei Lv ◽

Yanan Zhu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Lymphoblastic Leukemia ◽

Genetic Alteration ◽

Missense Mutations ◽

Nonsense Mutations ◽

Specific Distribution ◽

Aggressive Clinical Course ◽

Acute Myeloid

Abstract IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-alleleCEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.

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TRANSFORMING ACTIVITIES OF THE NUP98-KMT2A FUSION GENE ASSOCIATED WITH MYELODYSPLASIA AND ACUTE MYELOID LEUKEMIA

HemaSphere ◽

10.1097/02014419-201906001-00429 ◽

2019 ◽

Vol 3 ◽

pp. 218

Author(s):

J. N. Fisher ◽

A. Thanasopoulou ◽

S. Juge ◽

A. Tzankov ◽

F. O. Bagger ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Acute Myeloid

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A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11) in a patient with acute myeloid leukemia

Cancer Genetics and Cytogenetics ◽

10.1016/j.cancergencyto.2008.02.005 ◽

2008 ◽

Vol 183 (2) ◽

pp. 105-108 ◽

Cited By ~ 33

Author(s):

Gabriella Cirmena ◽

Stefania Aliano ◽

Giuseppina Fugazza ◽

Roberto Bruzzone ◽

Anna Garuti ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Acute Myeloid

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Sea-Blue Histiocytosis of Bone Marrow in a Patient with t(8;22) Acute Myeloid Leukemia

Case Reports in Oncology ◽

10.1159/000508495 ◽

2020 ◽

Vol 13 (2) ◽

pp. 849-852 ◽

Cited By ~ 1

Author(s):

Osamu Imataki ◽

Makiko Uemura

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Zinc Finger Protein ◽

Fusion Gene ◽

Monocytic Leukemia ◽

Non Hodgkin Lymphoma ◽

Old Japanese ◽

Characteristic Features ◽

Acute Myeloid

An 80-year-old Japanese male was treated with chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisolone, for non-Hodgkin lymphoma. Nine months after the chemotherapy, he was diagnosed with acute myeloid leukemia (AML) (M4) with translocation 8p11 and 22q13. The patient bone marrow indicated a remarkable degree of sea-blue histiocytosis. His disease was aggressive, and he died of the disease. Sea-blue histiocytes are macrophages harboring blue vacuoles and granular deposition, which results from the phagocytosis of dead cells and the subsequent deposition of phospholipids. AML with the t(8; 22) (p11; q13) translocation is a rare subtype of AML, which is a rare translocation with a prevalence of less than 1.0% among all AML cases. The oncogenesis of t(8; 22) (p11; q13) is caused by the fusion protein monocytic leukemia zinc finger protein (MOZ) and transcription factor p300. MOZ can be fused to various translocation targets including CBT, TIF2, and p300, corresponding to t(8; 16), inv(8), and t(8; 22), respectively. This subgroup of AML reveals the hallmarks of the disease, including monocytic arrest and erythro/hemophagocytosis by blasts. A substantial proportion of the AML M4/M5 subtype harboring MOZ as an aberrant fusion gene represents erythrophagocytosis. Although rare, t(8; 22) is very specific to the AML M4/M5 subtype and seems to represent sea-blue histiocytosis as one of the characteristic features of monocytic AML with macrophage activation. Thus, sea-blue histiocytes are considered to be one of hallmarks in monocytic AML with MOZ translocation.

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Identification of the UBA2-WTIP fusion gene in acute myeloid leukemia

Experimental Cell Research ◽

10.1016/j.yexcr.2018.08.035 ◽

2018 ◽

Vol 371 (2) ◽

pp. 409-416

Author(s):

Xiaoya Lu ◽

Haifeng Zhuang ◽

Qingfeng Yu ◽

Xuzhao Zhang ◽

Zhaoxing Wu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Acute Myeloid

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A case of pediatric acute myeloid leukemia with t(11;16)(q23;q24) leading to a novel KMT2A-USP10 fusion gene

Genes Chromosomes and Cancer ◽

10.1002/gcc.22646 ◽

2018 ◽

Vol 57 (10) ◽

pp. 522-524 ◽

Cited By ~ 2

Author(s):

Elena Zerkalenkova ◽

Svetlana Lebedeva ◽

Anna Kazakova ◽

Pavel Baryshev ◽

Claus Meyer ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Pediatric Acute Myeloid Leukemia ◽

Acute Myeloid

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PS1012 PREDICTING A PML-RARA FUSION GENE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA BY CONVOLUTIONAL NEURAL NETWORKS

HemaSphere ◽

10.1097/01.hs9.0000562344.99671.79 ◽

2019 ◽

Vol 3 (S1) ◽

pp. 455-456

Author(s):

C.-J. Liu ◽

Y.-C. Liu ◽

W. Yuan ◽

K.-H. Yu

Keyword(s):

Neural Networks ◽

Acute Myeloid Leukemia ◽

Convolutional Neural Networks ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Acute Myeloid

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The Angiogenic Factor Angiopoietin-1 Is Regulated by the Acute Myeloid Leukemia Fusion Protein AML1/ETO

Blood ◽

10.1182/blood.v118.21.2426.2426 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2426-2426

Author(s):

Victoria J Forster ◽

Patricia Garrido Castro ◽

Amy K Bradburn ◽

James M Allan ◽

Olaf Heidenreich

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Bone Marrow Niche ◽

Transcript Levels ◽

Qrt Pcr ◽

Acute Myeloid ◽

Angiopoietin 1

Abstract Abstract 2426 BACKGROUND The chromosomal rearrangement t(8;21)(q22;q22) encodes the fusion gene AML1/ETO, which is the most common translocation in acute myeloid leukemia (AML). It has an incidence of approximately 15% and a favourable prognosis in comparison to other AML subtypes. Dysregulated angiogenesis in the bone marrow niche environment is predicted to have an important role in leukemia pathogenesis, and several factors have been implicated in this process. Angiopoietin-1 (ANGPT1) is a cytokine involved in hematopoietic stem cell quiescence and regulation of microvessel density within the bone marrow, as well as having a role in transendothelial migration. Moreover, ANGPT1 is upregulated in leukemic blast cells from AML patients. In this study we investigated the role of AML1/ETO as a regulator of ANGPT1 expression, as well as functional implications of ANGPT1 in AML1/ETO-positive AML. METHODS In order to investigate putative AML1/ETO-dependent regulation of ANGPT1, we performed gain-of-function studies using lentiviral gene transfer to ectopically express AML1/ETO in HL-60 and U937 AML cell lines. We also depleted AML1/ETO in the t(8;21)-positive AML cell line Kasumi-1 using fusion gene specific siRNA. Additionally, the functional role of ANGPT1 was studied using targeted RNAi in Kasumi-1 cells. Transcript expression of AML1/ETO and ANGPT1 was analysed by quantitative Real-Time PCR (qRT-PCR) and AML1/ETO protein expression was quantified by western blotting. Angiopoietin-1 protein secretion was determined using enzyme-linked immunosorbent assay (ELISA). We also utilised Matrigel transwell assays to test the effect of ANGPT1 downregulation on the invasive and migratory properties of Kasumi-1. RESULTS In HL-60 and U937 transduced with AML1/ETO, we observed an up to 280 fold increase in ANGPT1 mRNA transcript levels as measured by qRT-PCR, which correlated with an increase in secreted Angiopoietin-1 protein. Conversely, siRNA-mediated AML1/ETO depletion in Kasumi-1 cells significantly decreased ANGPT1 transcript and protein levels after a single electroporation. After three serial electroporations with siRNA, AML1/ETO transcript levels were reduced by 85%, with a concomitant decline in ANGPT1 transcript (>99%) and secreted protein. Preliminary data suggest siRNA targeting of ANGPT1 in Kasumi-1 decreases the invasive ability of these cells, causing a ≥50% reduction in invasion when compared to controls. CONCLUSIONS We have identified a strong correlation between AML1/ETO and ANGPT1 expression, whereby a reduction of AML1/ETO results in a substantial reduction of ANGPT1. Similarly, the introduction of AML1/ETO into myeloid cell lines results in a large upregulation of ANGPT1. Preliminary evidence suggests that a reduction of ANGPT1 reduces the invasive and migratory potential of Kasumi-1. This could have major functional consequences in the bone marrow niche with regards to understanding the AML stem cell and its interaction with the niche environment as well as providing insight into how leukemic cells in the circulation might interact with the vasculature. Disclosures: No relevant conflicts of interest to declare.

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