scholarly journals Assessment of The Lnc-CCAT1/miR-155a Regulatory Network in Acute Myeloid Leukemia

2019 ◽  
pp. 1-8
Author(s):  
Nashwa EL-Khazragy ◽  
Magdy Mohamed ◽  
Rehab Abdelmaksoud ◽  
Eman Saleh

Colon cancer-associated transcript_1 (CCAT1) is a long noncoding RNA that maps to chromosome 8q24.21, it was first discovered to be upregulated in colorectal cancer. Recent studies have observed the CCAT1 overexpression in primary human solid cancers and cell lines as well as in AML, moreover, it repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. However, the prognostic value of CCAT1/miR-155a pathway in acute myeloid Leukemia (AML) has not been investigated on clinical samples. In this study, the expression levels of CCAT1 and miR_155a was measured in 150 AML patients with standard and high-risk factors; CCAT1 and miR_155a were increased by 2.7 and 5.7 folds; respectively in AML compared to healthy controls. Furtherly, upregulation of both biomarkers was significantly associated with high risk AML. Collectively, these results suggest that CCAT1 and miR_155a can be considered as a diagnostic and prognostic biomarker in AML.

2018 ◽  
Vol 36 (15) ◽  
pp. 1486-1497 ◽  
Author(s):  
Sylvie D. Freeman ◽  
Robert K. Hills ◽  
Paul Virgo ◽  
Naeem Khan ◽  
Steve Couzens ◽  
...  

Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD−. Patients without high-risk factors, including Flt3 internal tandem duplication wt/− NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival [OS], 27% RD v 46% PR v 51% MRD+ v 70% MRD−; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio [HR], 1.88 [95% CI, 1.50 to 2.36], P < .001; survival: HR, 1.77 [95% CI, 1.41 to 2.22], P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD−, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD− (HR, 1.68 [95% CI, 0.75 to 3.85]; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR.


2019 ◽  
Author(s):  
Sai Huang ◽  
Zhi Huang ◽  
Chao Ma ◽  
Lan Luo ◽  
Yan-fen Li ◽  
...  

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S107-S108
Author(s):  
A C Reddy ◽  
K S Reddy

Abstract Introduction/Objective Histiocytic sarcoma (HS) is rare (&lt;1% of hematolymphoid neoplasms), and can present extranodally as disseminated disease. Immunophenotypically, the cells express CD163, CD68, lysozyme and CD45. HS often occurs as a secondary event following B-cell lymphomas, acute lymphoblastic leukemia or acute myeloid leukemia (AML) typically with monocytic differentiation retaining the same molecular/cytogenetic abnormalities as the primary tumor. Results Our patient, a 47 year old male was diagnosed with myeloid sarcoma (MS) following FNA of a new neck mass. A bone marrow biopsy revealed AML without monocytic differentiation. Flow cytometric findings of both marrow and neck mass were similar (positive for CD34, CD117, CD33, CD11b, CD13, CD15, CD64, CD7; negative for CD4, CD14, CD56). Karyotypic and FLT3 ITD mutation analysis were normal. CNS involvement was diagnosed 2 months later, while a marrow biopsy (status post therapy) confirmed resolution of AML. A hypermetabolic left perinephric mass noted by PET CT, when biopsied, showed large epithelioid polygonal cells with amphophilic cytoplasm and atypical vesicular nuclei (positive for CD68, PU.1; negative for LCA, CD163, CD34, CD4, pankeratin). A diagnosis of atypical epithelioid neoplasm suggestive of HS was rendered, although negativity for LCA and CD163 was unusual. No treatment was given for HS. A month later, the patient presented with a cheek mass diagnosed again as being suggestive of HS. His AML also relapsed. Next-generation sequencing (37 genes including BRAF) from both marrow and tissue samples detected the presence of a nonsense mutation in exon 7 of WT1 (p.Ser169). Conclusion Our case appears to be the first reported one of disseminated HS preceded by MS and concomitant AML, lacking monocytic differentiation. The findings overall support the hypothesis of origin as being from a common progenitor cell differentiating along both myeloid and histiocytic/other cell lineages at different time points.


Author(s):  
Aliihsan Gemici ◽  
Fahir Ozkalemkas ◽  
Mehmet Hilmi Dogu ◽  
Atakan Tekinalp ◽  
Inci Alacacioglu ◽  
...  

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