scholarly journals Comparison of spatial chromosomal organization between bone marrow and peripheral blood in acute myeloid leukemia

2018 ◽  
Author(s):  
Xueli Tian ◽  
Yanfang Wang ◽  
Yu Liu ◽  
Jun Yin ◽  
Dieyan Chen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chromosomal Organization ◽  
Acute Myeloid

Detection of Nucleophosmin Gene Mutations in Plasma from Patients with Acute Myeloid Leukemia: Clinical Significance and Implications.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2855-2855
Author(s):  
Wanlong Ma ◽  
Xi Zhang ◽  
Iman Jilani ◽  
Farhad Ravandi ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Leukemic Cells ◽  
Striking Difference ◽  
Plasma Dna ◽  
Npm1 Mutation ◽  
Acute Myeloid

Abstract Nucleotides insertion in the nucleophosphamin (NPM1) gene has been reported in about one third of patients with acute myeloid leukemia (AML). Multiple studies showed that the presence of NPM1 mutations associated with better outcome in patients with AML. Studies reported to date have analyzed leukemic cells obtained from bone marrow or peripheral blood. We tested for mutations in the NPM1 gene using peripheral blood plasma and compared results with clinical outcome from a single institution. Analyzing plasma from 98 newly diagnosed patient with AML showed NPM1 mutation in 24 (23%) of patient while only one (4%) of 28 previously untreated patients with myelodysplastic syndrome (MDS) showed NPM1 mutation. Compared with peripheral blood cells, 2 (8%) of the 24 positive patients were negative by cells; none were positive by cells and negative by plasma. Most of the mutations detected (45%) were in patients with FAB classification M2, M4 and M5. In addition to the reported 4 bp insertion, we also detected 4 bp deletion in one patient in cells and plasma. Patients with NPM1 mutation had a significantly higher white blood cell count (P = 0.0009) and a higher blast count in peripheral blood (P = 0.002) and in bone marrow (P = 0.002). Blasts in patients with NPM1 mutant expressed lower levels of HLA-DR (P = 0.005), CD13 (P = 0.02) and CD34 (P < 0.0001), but higher CD33 levels (P = 0.0004). Patients with NPM1 mutation appear to have better chance of responding to standard therapy (P = 0.06). Event free survival of patients with NPM1 mutation was longer (P = 0.056) than in patients with intermediate cytogenetic abnormalities. The most striking difference in survival was in patients who required >35 days to respond to therapy (Figure). Survival was significantly longer in patients with NPM1 mutation requiring >35 days to respond (P = 0.027). This data not only support that NPM1 plays a significant role in the biology and clinical behavior of AML, but also show that plasma DNA is enriched with leukemia-specific DNA and is a reliable source for testing. Figure Figure

scholarly journals Different regulation of PARP1, PARP2, PARP3 and TRPM2 genes expression in acute myeloid leukemia cells

2019 ◽  
Author(s):  
Paulina Gil-Kulik ◽  
Ewa Dudzińska ◽  
Elżbieta Radzikowska-Büchner ◽  
Joanna Wawer ◽  
Mariusz Jojczuk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Mrna Level ◽  
Hematopoietic Stem ◽  
Genes Expression ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogenic lethal disorder characterized by the accumulation of abnormal myeloid progenitor cells in the bone marrow, which results in hematopoietic failure. Despite various efforts in detection and treatment, many patients with AML die of this cancer. That is why it is important to develop novel therapeutic options, employing strategic target genes involved in apoptosis and tumor progression. The aim of the study was to evaluate PARP1, PARP2, PARP3, and TRPM2 gene expression at the mRNA level in the cells of the hematopoietic system of the bone marrow in patients with acute myeloid leukemia, bone marrow collected from healthy patients, peripheral blood of healthy individuals, and hematopoietic stem cells from the peripheral blood after mobilization.Results: The results found that the bone marrow cells of patients with acute myeloid leukemia (AML) show over expression of PARP1 and PARP2 genes and decreased TRPM2 gene expression. In the hematopoietic stem cells derived from the normal marrow and peripheral blood after mobilization, the opposite situation was observed, i.e. TRPM2 gene showed increased expression while PARP1 and PARP2 gene expression was reduced. We observed the positive correlations between PARP1, PARP2, PARP3, and TRPM2 genes expression in the group of mature mononuclear cells derived from the peripheral blood and in the group of bone marrow-derived cells. In AML cells significant correlations were not observed between the expression of the examined genes.Conclusions: Our research suggests that in physiological conditions in the cells of the hematopoietic system there is mutual positive regulation of PARP1, PARP2, PARP3, and TRPM2 genes expression. PARP1, PARP2, and TRPM2 genes at mRNA level deregulate in acute myeloid leukemia cells.

scholarly journals A Robust Xenotransplantation Model for Acute Myeloid Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2939-2939
Author(s):  
Robin L. Perry ◽  
Patricia Vanessa Sanchez ◽  
Jean-Emmanuel Sarry ◽  
Alexander Perl ◽  
Adam Bagg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chemotherapeutic Agents ◽  
Murine Bone Marrow ◽  
Cell Engraftment ◽  
Nog Mice ◽  
Xenotransplantation Model ◽  
Acute Myeloid

Abstract Xenotransplantation of human acute myeloid leukemia (AML) in immunocompromised animals has been critical for the definition of leukemic stem cells. However, existing immunodeficient strains such as NOD/SCID and NOD/SCID/b2mnull have short life spans, age dependent leakiness of humoral immunity and low levels of AML cell engraftment making long-term evaluation of primary human AML biology difficult. A recent study suggested that the nonobese diabetic/severe combined immondeficient/IL2Rgnull (NOG) mouse has enhanced ability to engraft AML cells but this study relied on neonatal injections that are technically challenging. We performed an extensive analysis of AML engraftment in adult NOG mice using intravenous tail vein injection. Thirty-six different AML samples were analyzed including 2 samples of acute promyelocytic leukemia (APML). We used a threshold for AML engraftment of &gt;0.5% human CD45+33+ cells in the murine bone marrow. Based on this threshold, 22 samples (61%) showed engraftment in NOG mice. Of these samples, 14 (64%) showed high levels of engraftment (greater than 10% of murine marrow replaced with human CD45+CD33+ cells). Engraftment did not correlate with FAB subtype or cytogenetic abnormalities to a statistically significant degree, however we noted that one sample with an 11q23 translocation and several samples with Flt3 ITD mutations showed consistent high level engraftment. Several samples demonstrated engraftment as high as 95% of the murine marrow with total AML cell expansion of 2-30 fold. Evaluation of AML stem cell frequency and expansion is ongoing. Engraftment in spleen was variable and in general significantly lower than in bone marrow. For most samples, peripheral blood engraftment was barely detectable. In contrast to NOD/SCID mice, both APML samples engrafted well in the NOG mouse with high levels of peripheral blood involvement. Some samples occasionally showed engraftment of a population of cells expressing CD2 and other T cell associated markers by flow cytometry, however this observation was inconsistent even between mice injected with the same sample. All samples tested (n=5) showed consistent engraftment in secondary and tertiary recipients with most samples tested showing further expansion of total AML cells in subsequent transplants. Importantly, a number of animals developed organomegaly and a wasting illness consistent with advanced leukemic disease. Several such animals showed extramedullary leukemic infiltration into non-hematopoietic tissues. Etoposide monotherapy (40 mg/kg in divided doses) of heavily engrafted mice did not induce a significant response in terms of leukemia regression. Studies of other chemotherapeutic agents are ongoing. We conclude that the NOG xenotransplantation model is a robust model for studying human AML cell engraftment which will allow for better characterization of AML biology and testing of new therapies

scholarly journals Hematologic Presentations of COVID-19 Can be Misinterpreted as Acute Myeloid Leukemia

2021 ◽  
Vol 6 (3) ◽  
pp. 231-233
Author(s):  
Hedieh Moradi Tabriz ◽  
Elham Nazar ◽  
Fatemeh Jazayeri ◽  
Arezoo Eftekhar Javadi
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Inflammatory Responses ◽  
White Blood Cells ◽  
Laboratory Data ◽  
Human Beings ◽  
Cytopathic Effects ◽  
Acute Myeloid

Introduction: COVID-19 infection prompts inflammatory responses and acute lung injury in human beings. Complete blood count with differential is essential investigative tool in its managing. However, very few studies revealed the variations of blood cell morphology in this disease.Case report: We reported a 39-years- old female patient complained of respiratory distress one week prior to hospitalization. The patient suffered from cough, fever, and molecular test was reported positive for COVID-19 infection. Laboratory data revealed severe permanent leukopenia and peripheral blood smear examination showed blastoid cells after remission of respiratory signs. Patient underwent bone marrow biopsy for rule out acute myeloid leukemia. But, on bone marrow sample, only viral cytopathic effects were seen. COVID-19 virus stimulates inflammatory cells to produces various inflammatory cytokines and as a result, viral cytopathic effects on white blood cells is seen. Conclusion: We have described how the characteristic peripheral blood findings of COVID‐19 infection can be misinterpret as acute myeloid leukemia.

scholarly journals Different regulation of PARP1, PARP2, PARP3 and TRPM2 genes expression in acute myeloid leukemia cells

2020 ◽  
Author(s):  
Paulina Gil-Kulik ◽  
Ewa Dudzińska ◽  
Elżbieta Radzikowska-Büchner ◽  
Joanna Wawer ◽  
Mariusz Jojczuk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Mrna Level ◽  
Hematopoietic Stem ◽  
Genes Expression ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is a heterogenic lethal disorder characterized by the accumulation of abnormal myeloid progenitor cells in the bone marrow which results in hematopoietic failure. Despite various efforts in detection and treatment, many patients with AML die of this cancer. That is why it is important to develop novel therapeutic options, employing strategic target genes involved in apoptosis and tumor progression.Methods: The aim of the study was to evaluate PARP1, PARP2, PARP3, and TRPM2 gene expression at mRNA level using qPCR method in the cells of hematopoietic system of the bone marrow in patients with acute myeloid leukemia, bone marrow collected from healthy patients, peripheral blood of healthy individuals, and hematopoietic stem cells from the peripheral blood after mobilization. Results: The results found that the bone marrow cells of the patients with acute myeloid leukemia (AML) show overexpression of PARP1 and PARP2 genes and decreased TRPM2 gene expression. In the hematopoietic stem cells derived from the normal marrow and peripheral blood after mobilization, the opposite situation was observed, i.e. TRPM2 gene showed increased expression while PARP1 and PARP2 gene expression was reduced. We observed positive correlations between PARP1, PARP2, PARP3, and TRPM2 genes expression in the group of mature mononuclear cells derived from the peripheral blood and in the group of bone marrow-derived cells. In AML cells significant correlations were not observed between the expression of the examined genes. In addition, we observed that the reduced expression of TRPM2 and overexpression of PARP1 are associated with a shorter overall survival of patients, indicating the prognostic significance of these genes expression in AML.Conclusions: Our research suggests that in physiological conditions in the cells of the hematopoietic system there is mutual positive regulation of PARP1, PARP2, PARP3, and TRPM2 genes expression. PARP1, PARP2, and TRPM2 genes at mRNA level deregulate in acute myeloid leukemia cells.

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