scholarly journals High correlation of the proteome patterns in bone marrow and peripheral blood blast cells in patients with acute myeloid leukemia

2009 ◽  
Vol 7 (1) ◽  
Author(s):  
Gero Hütter ◽  
Anne Letsch ◽  
Daniel Nowak ◽  
Julia Poland ◽  
Pranav Sinha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Blast Cells ◽  
Acute Myeloid

Cellular pharmacokinetics of daunorubicin: relationships with the response to treatment in patients with acute myeloid leukemia.

1988 ◽  
Vol 6 (5) ◽  
pp. 802-812 ◽  
Author(s):  
E Kokenberg ◽  
P Sonneveld ◽  
W Sizoo ◽  
A Hagenbeek ◽  
B Löwenberg
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Response To Treatment ◽  
Remission Induction ◽  
Pharmacokinetic Parameters ◽  
Induction Treatment ◽  
Blast Cells ◽  
Acute Myeloid

In an attempt to identify pharmacokinetic factors that determine the response of acute myeloid leukemia (AML) patients to induction chemotherapy, we determined the concentrations of daunorubicin (DNR) and the main metabolite daunorubicinol (DOL) in vivo and particularly evaluated the concentrations in blood and bone marrow nucleated cells. Cell measurements were obtained in 37 evaluable patients during their first remission induction treatment with DNR and cytarabine (ara-C) and directly compared with the plasma distribution kinetics of DNR. We show that (1) plasma DNR concentrations do not correlate with DNR concentrations in bone marrow nucleated cells; but (2) plasma area under the curve (AUC) values of DNR correlate inversely (P less than .01) with AUC values of DNR in WBCs; (3) concentrations of DNR in WBCs correlate positively (P less than .01) with DNR concentrations in bone marrow nucleated cells; and (4) the concentrations of DNR in WBCs show a negative correlation (P less than .01) with the numbers of peripheral blast cells at diagnosis. We then tested whether the pharmacokinetic parameters had predictive value for the clinical outcome of therapy, but none of the plasma levels or WBC and bone marrow concentrations of DNR predicted treatment outcome. The inverse correlation between the concentrations of DNR in WBC and the numbers of peripheral blast cells suggests that the effective DNR concentrations achieved intracellularly are mainly a function of the tumor load so that lesser amounts of DNR accumulate intracellularly when the AML cell numbers in blood are higher.

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

TIM-3 Is Highly Expressed On Blast Cells In Patients With Acute Myeloid Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4931-4931
Author(s):  
Caixia Li ◽  
Xiao Yu ◽  
Yibei Zhu ◽  
Xiaojin Wu ◽  
Xiao Ma ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Negative Regulator ◽  
Clinical Implications ◽  
Potential Marker ◽  
Blast Cells ◽  
Acute Myeloid

Abstract T cell immunoglobulin-3(TIM-3) is known as a negative regulator in anti-tumor immunity through its reaction with TIM-3 ligand, galectin-9. It has been confirmed that TIM-3 is expressed on Th1 cells, dendritic cells, monocytes, macrophages, malignant stem cells and so on. But the expression of TIM-3 and its clinical implications in patients with acute myeloid leukemia(AML) remains unknown. In this study, we sought to determine the expression and clinical implications of TIM-3 in AML. From August 2012 to June 2013, in total of 32 AML patients with sixteen male and sixteen female were enrolled in this study. We collected their peripheral blood before they received any treatment and then obtained their peripheral blood mononuclear cells(PBMC). Monoclonal antibody was added into PBMC and cell population was analyzed by flow cytometry. Blast cells were identified with SSC CD45±and mature lymphocytes with SSC CD45+. The average expression of TIM-3 on blast cells was 43.46%, while on mature lymphocytes was 13.78% (P<0.001). In univariate analysis, the level of expression was not correlated to the percentage of blast cells and there was no difference between each type of AML. Complete remission was similar between different levels of TIM-3 expression(P>0.05). These results demonstrated that TIM-3 was highly expressed on blast cells than on mature cells in AML, which indicated that TIM-3 could be associated with the differentiation of blast cells and a potential marker to detect the tendency of relapse. TIM-3-targeted antitumor therapy presents a perspective possibility. Disclosures: No relevant conflicts of interest to declare.

Acute Myeloid Leukemia In Patient Over 90 Years Old: Where Do We Go From Here? Case Report

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5034-5034 ◽  
Author(s):  
Marcelo Bellesso ◽  
Daniela Ferreira Dias ◽  
Renato Centrone ◽  
Rodrigo Santucci ◽  
Izabel Pernambuco Nicodemo
Keyword(s):  
Quality Of Life ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Aspirate ◽  
Chronological Age ◽  
Acceptable Quality ◽  
Blast Cells ◽  
Acute Myeloid

Abstract Introduction Acute Myeloid Leukemia (AML) widely affects elderly patients, with disappointing survival rates with increasing age. Although chronological age is an independent prognostic risk, it is really important to understand that this group is heterogeneous, so a geriatric assessment may be helpful before making decisions regarding therapy. We describe a 91 year-old patient with AML treated with decitabine, achieving a complete response and good quality of life for 10 months. Case Report In May 2012, a 91 year-old woman with myelodysplastic syndrome was admitted at the emergency department presenting asthenia, pallor, pain and edema of the left inferior limb. Her blood count showed: hemoglobin 10.7g/dL, leukocytes 81.800/mm³ with 95% blast cells, and platelets 45.000/mm³. In addition, a Doppler ultrasound evidenced deep venous thrombosis in her left leg. A bone marrow aspirate confirmed AML with myelodysplasia-related alterations, with 95% blast cells, with positive expression of CD45, CD33, MPO, and CD117 (CD45+; CD33+; MPO+; CD117+). Her karyotype was 46,XX [20 cells analyzed]. She was first treated with hydroxyurea. Afterwards, as her performance status improved and in spite of her age, we decided to treat her with Decitabine 20mg/m²/day for 5 days, because she had no severe comorbidity or any severe impairment of every-day-life instrumental activities. After a first cycle with grade 4 neutropenia and thrombocytopenia, she was discharged. After 40 days, complete hematologic recovery was observed. She received seven treatment cycles, and the most important symptom of toxicity was febrile grade 3 neutropenia in the 3rd cycle, with the only inpatient treatment. After this intercurrence, the doses were reduced by 25%. The patient achieved complete remission, spent eleven months without needing blood transfusions and with an acceptable quality of life, but then she relapsed, presenting persistent neutropenia and 44% of blasts in a bone marrow aspirate (05/27/2013). She died on 07/02/2013 due to the progression of the disease. Conclusion This case shows that, despite her advanced chronological age, our patient, affected by a fatal disease, lived approximately 13 months with optimal response to treatment (with Decitabine) and enjoying an acceptable quality of life for ten months. Considering this patient profile, could we conclude that this outcome is the best our treatment can aim to achieve? Disclosures: No relevant conflicts of interest to declare.

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.

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