.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2372-2372 ◽  
Author(s):  
Peter Dean Emanuel ◽  
Zhuo Wang ◽  
Danying Cai ◽  
Mary R. Stofega ◽  
James G. Keck ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Regulatory Element ◽  
Hematological Parameters ◽  
Hematopoietic Progenitor Cell ◽  
Glutathione S Transferase ◽  
Cell Counts ◽  
Proliferation And Differentiation ◽  
Before And After ◽  
Myeloid Progenitor Cells

Abstract TLK199 is a novel glutathione analog that is a selective inhibitor of the enzyme glutathione S-transferase (GST) P1-1. TLK199 treatment induces hematopoietic cell proliferation and differentiation through activation of the MAP kinase signaling pathway leading to activation of JNK and ERK2. In rodent models of chemotherapy induced neutropenia, treatment with TLK199 accelerated recovery of white cell counts at rates comparable to treatment with G-CSF. We now report TLK199 treatment of myeloid progenitor cells isolated from normal human blood resulted in the increased formation of CFU-GM (46%) CFU-MK (47%) and BFU-E (142%) lineages over baseline. A corresponding increase in the percentage of cells expressing CD11b, a granulocyte and monocyte marker, was observed in the CFU-GM cells. Since TLK199 is currently being evaluated in a Phase 2a trial in patients with refractory MDS, we examined the effect of treatment on formation of BFU-E, CFU-GM and CFU-GEMM before and after TLK199 treatment at doses of 50 to 400 mg/m2. A significant increase in the number of hematopoietic progenitor cell colonies measured from patient peripheral blood and bone marrow was observed as early as Day 4 of Cycle 1 as compared to pretreatment baseline. Ten of 12 patients showed an increase in at least one colony forming type (BFU-E, CFU-GM and CFU-GEMM) and 7 of 12 had an increase in all three colony forming types following TLK199 administration. These results correlate with clinical improvement in hematological parameters in peripheral blood and bone marrow observed in MDS patients treated with TLK199. Studies are underway to define the mechanism of bone marrow and peripheral blood count recovery observed following treatment of MDS patients with TLK199 and the role of GST P1-1 as a regulatory element in myeloid proliferation and differentiation.

scholarly journals Protective effects of rosmarinic acid against radiation-induced damage to the hematopoietic system in mice

2016 ◽  
Vol 57 (4) ◽  
pp. 356-362 ◽  
Author(s):  
Wenqing Xu ◽  
Fujun Yang ◽  
Yujie Zhang ◽  
Xiu Shen
Keyword(s):  
Bone Marrow ◽  
Dna Content ◽  
Peripheral Blood ◽  
Rosmarinic Acid ◽  
Hematological Parameters ◽  
Whole Body ◽  
Control Group ◽  
Hematopoietic System ◽  
Treatment Groups ◽  
Cell Counts

Abstract Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid. It is a potent antioxidant that functions by scavenging free radicals. Here, we used a 30-day survival assay to investigate the radioprotective effects of RA. Mice were treated with RA once per day for 10 consecutive days starting at 3 days before gamma irradiation at 7.5 Gy until 7 days post irradiation. Mice treated with 100 and 200 mg/kg body weight (bw) of RA had 30-day survival rates of 89% and 72%, respectively, compared with 32% in the control group, and the differences were statistically significant ( P = 0.0008 and 0.0421, respectively). Spleen colony–forming units (CFU-S), the number of nucleated cells in the bone marrow (BMNC), bone marrow DNA content, and hematological parameters of the peripheral blood were measured to investigate the radioprotective effect of RA on the hematopoietic system. The treatment groups that received RA at 50, 100 and 150 mg/kg bw and whole-body exposure to 5.5 Gy of 137 Cs γ- radiation had significantly higher CFU-S, BMNC and DNA content than the irradiation-only group. Assessment of hematological parameters in the peripheral blood showed that the treatment groups receiving RA at doses of 50, 100 and 150 mg/kg bw had higher white blood cell counts, hemoglobin and platelets than the radiation-only group. These results suggested that the administration of RA promoted the recovery of peripheral blood cells in irradiated mice.

scholarly journals Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine

Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1443-1447
Author(s):  
WJ Murphy ◽  
G Tsarfaty ◽  
DL Longo
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
Growth Hormone ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Cell Content ◽  
Cell Counts ◽  
Growth Promoting

Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content and cellularity, indicating that rhGH can act as a hematopoietic growth factor. C57BL/6 mice were then placed on azidothymidine (AZT). AZT is a reverse transcriptase inhibitor currently used as a treatment for acquired immune deficiency syndrome (AIDS), but which also produces significant myelotoxic effects. Treatment of mice with rhGH partially counteracted the myelosuppressive properties of AZT. Bone marrow cellularity, hematocrit values, white blood cell counts, and splenic hematopoietic progenitor cell content were all significantly increased if rhGH (20 micrograms injected intraperitoneally every other day) was concurrently administered with AZT. Administration of ovine GH (ovGH), which, unlike rhGH, has no effect on murine prolactin receptors, also prevented the erythroid-suppressive effects of AZT in mice, but had no significant effect on granulocyte counts. Thus, the effects of GH are mediated at least in part through GH receptors in vivo. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of ovGH resulted in an increase in splenic hematopoietic progenitor cells. No significant pathologic effects were observed in mice receiving either repeated rhGH or ovGH injections. Thus, GH exerts significant direct hematopoietic growth-promoting effects in vivo and may be of potential clinical use to promote hematopoiesis in the face of myelotoxic therapy.

scholarly journals Proliferation and differentiation potential of CD133+ and CD34+ populations from the bone marrow and mobilized peripheral blood

2010 ◽  
Vol 90 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Irena Koutna ◽  
Martina Peterkova ◽  
Pavel Simara ◽  
Stanislav Stejskal ◽  
Lenka Tesarova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Differentiation Potential ◽  
Proliferation And Differentiation ◽  
Mobilized Peripheral Blood

Correlation Between Changes of Pelvic Bone Marrow Fat Content and Hematological Toxicity in Concurrent Chemoradiotherapy for Cervical Cancer

2021 ◽  
Author(s):  
Cong Wang ◽  
Xiaohang Qin ◽  
Guanzhong Gong ◽  
Lizhen Wang ◽  
Ya Su ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Bone Marrow ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Concurrent Chemoradiotherapy ◽  
Peripheral Blood Cell ◽  
Fat Content ◽  
Pelvic Bone ◽  
Cell Counts ◽  
Blood Cell Counts

Abstract Objectives: To quantify the pelvic bone marrow (PBM) fat content changes receiving different radiation doses of concurrent chemoradiotherapy for cervical cancer and to determine association with peripheral blood cell counts. Methods: Fifty-four patients were prospectively collected. Patients underwent MRI iterative decomposition of water and fat with echo asymmetrical and least squares estimation (IDEAL IQ) scanning at RT-Pre, RT mid-point, RT end, and six months. The changes in proton density fat fraction (PDFF%) at 5–10 Gy, 10–15 Gy, 15–20 Gy, 20–30 Gy, 30–40 Gy, 40–50 Gy, and >50 Gy doses were analyzed. Spearman’s rank correlations were performed between peripheral blood cell counts versus the differences in PDFF% at different dose gradients before and after treatment. Results: The lymphocytes (ALC) nadirs appeared at the midpoint of radiotherapy, which was only 27.6% of RT-Pre; the white blood cells (WBC), neutrophils (ANC), and platelets (PLT) nadirs appeared at the end of radiotherapy which was 52.4%, 65.1%, and 69.3% of RT-Pre, respectively. At RT mid-point and RT-end, PDFF% increased by 46.8% and 58.5%, respectively. Six months after radiotherapy, PDFF% decreased by 4.71% under 5–30 Gy compared to RT-end; while it still increased by 55.95% compared to RT-Pre. There was a significant positive correlation between PDFF% and ANC nadirs at 5–10 Gy (r = 0.62, P = 0.006), and correlation was observed between PDFF% and ALC nadirs at 5–10 Gy (r = 0.554, P = 0.017). Conclusion: MRI IDEAL IQ imaging was a non-invasive approach to evaluate and track the changes of PBM fat content with concurrent chemoradiotherapy for cervical cancer. The limitation of low-dose bone marrow irradiation volume in cervical cancer concurrent chemoradiotherapy should be paid more attention.

scholarly journals Effect of Feed Restriction on Peripheral Blood and Bone Marrow Cell Counts of Wistar Rats

1985 ◽  
Vol 34 (4) ◽  
pp. 407-416 ◽  
Author(s):  
Yukio OGAWA ◽  
Kiyoshi MATSUMOTO ◽  
Eiichi KAMATA ◽  
Yasukazu IKEDA ◽  
Toyozo KANEKO
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Peripheral Blood ◽  
Wistar Rats ◽  
Marrow Cell ◽  
Feed Restriction ◽  
Cell Counts

scholarly journals Administration of recombinant human interleukin-7 alters the frequency and number of myeloid progenitor cells in the bone marrow and spleen of mice

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1121-1129 ◽  
Author(s):  
G Damia ◽  
KL Komschlies ◽  
CR Faltynek ◽  
FW Ruscetti ◽  
RH Wiltrout
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Peripheral Blood Lymphocytes ◽  
Lymphoid Cells ◽  
Blood Leukocytes ◽  
Interleukin 7 ◽  
Immature B Cells ◽  
Myeloid Progenitor Cells ◽  
Phenotype Analysis

Abstract The administration of greater than or equal to 5 micrograms interleukin- 7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resulted in a greater than 90% reduction in the frequency and total number of single lineage colony- forming unit-culture (CFU-c) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte colonies that could be cultured from the BM, but a fivefold to 15-fold increase in the number of these progenitors that could be cultured from the spleen. All of these effects were reversible with progenitor and white blood cell numbers returning to near normal by day 6. Morphologic analysis of cells obtained from the BM of IL-7-treated mice showed an increase in lymphoid cells. Surface phenotype analysis showed that most of this IL- 7-induced increase in lymphocytes was attributable to an increase in immature B cells (B220+, sIg-), while cells expressing the myelomonocytic markers 8C5 and MAC-1 decreased by twofold to threefold. Further studies showed that the administration of IL-7 to mice that had been rendered leukopenic by the injection of cyclophosphamide (Cy) or 5- fluorouracil (5FU) exhibited a more rapid recovery and/or overshoot in their peripheral blood lymphocytes when compared with mice treated with Cy or 5FU alone. These results show that IL-7 can differentially regulate myelopoiesis in the BM and spleen, while stimulating lymphopoiesis.

WT1-Peptide Vaccination Shows High Immunogenicity and Clinical Activity in Patients with Acute Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 406-406 ◽  
Author(s):  
Keilholz Ulrich ◽  
Carmen Scheibenbogen ◽  
Anne Letsch ◽  
Anne Marie Asemissen ◽  
Wolf Karsten Hofmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
High Risk ◽  
Clinical Outcome ◽  
Peripheral Blood ◽  
Great Promise ◽  
Clinical Activity ◽  
Peptide Vaccination ◽  
Before And After ◽  
Disease Stabilization

Abstract BACKGROUND: The transcription factor Wilms tumor protein 1 (WT1) holds great promise for immunotherapy of leukemia. WT1 is strongly expressed in the majority of leukemic blasts, is essential for blast proliferation, and is spontaneously immunogenic. METHODS: In the present phase II trial, 12 HLA-A2+ patients with AML without curative treatment option, were vaccinated with WT1.126–134 peptide mixed with adjuvant KLH as T-helper protein and GM-CSF 4 times bi-weekly, then monthly. RESULTS: Patients characteristics, immune responses and clinical outcome are shown in table 1. Patient characteristics, immunologic response, and clinical outcome Pat FAB/caryotype previous chemotherapy disease status at study onset no. of vaccinations clinical outcome WT1Tetr+ T cells in PB after vaccination WT1Tetr+ T cells in BM after vaccination *PB, peripheral blood; BM, bone marrow; MDS, myelodysplastic syndrome; MPD, myeloproliferative disease. 1 M4 yes 2.PR 15 CR 12 months 0.49% 0.87% 2 M2 11q23 yes 1.CR 18 cCR 30+ months 0.43% 0.91% 3 M2 no PD 4 SD 3 months 0.42% 0.80% 4 M6 yes PD 4 PD neg. neg. 5 M2 yes 1.PR 6 PD 0.37% 0.51% 6 M1 yes 2. PR 9 PD 0.43% 0.40% 7 M2 yes 2.PR 9 PD 2.00% 1.36% 8 M7 yes PD 4 PD neg. neg. 9 M5b yes 2.CR 12 cCR 8+ months 0.44% 0.33% 10 sAML from MDS no PD 12 SD 8 months 0.23% 0.13% 11 sAML from MPS no PD 12 SD 9+ months 0.22% 0.53% 12 M4 no PD 8 SD 3 months 1.11% 1.35% WT1-specific T cells could be detected in 3 patients before vaccination. An induction or enhancement of a T cell response against WT1 was observed in 10 of 12 patients after 2 – 6 vaccinations ranging from 0.22 to 2.00% (median 0.43%) in peripheral blood and from 0.33 to 1.36% (median 0.80%) in bone marrow as analysed by tetramer and cytokine staining. At study onset 6 patients had progressive AML (PD) with 40 – 90% marrow blasts, 4 patients partial remission (PR) following chemotherapy and two patients complete remission (CR) at high risk for relapse. Four of the 6 patients with progressive AML had disease stabilization for 3, 3, 8 and 9 months, which is ongoing in the latter patient. Disease stabilization was accompanied by a decrease/normalization of peripheral blasts in two patients and a >50% decrease in RBC transfusion requirements in a patient with AML evolved from MDS. One patient with PR at study onset had an early relapse and then achieved CR for 12 months (patient 1). Both patients vaccinated in CR are in continuous hematological CR (cCR) for 8+ and 30+ months (patient 2 and 9). The remaining 5 patients had PD after 4 – 9 vaccinations. Bone marrow WT1 RNA levels as molecular disease marker paralleled the clinical course as they decreased 1 – 2 logs in the 3 patients with CR or cCR after 6 vaccinations (Fig. 1A), stabilized or decreased in all 4 patients with SD (Fig. 1B), and increased 1 – 2 logs in 4 of the 5 patients with PD (Fig. 1B). No significant toxic effects were observed. CONCLUSION: WT1 peptide vaccination can efficiently induce a specific immune response and has clinical activity in the absence of significant toxicity. These results warrant further studies of WT1 vaccination in AML patients at high risk for relapse. Fig. 1 WT1 levels in bone marrow before and after 6 vaccinations in patients with CR or cCR (A), SD (B) or PD (C) after vaccination. Fig. 1. WT1 levels in bone marrow before and after 6 vaccinations in patients with CR or cCR (A), SD (B) or PD (C) after vaccination.

Peripheral Blood Cytogenetic Studies in Hematological Neoplasms: Predictors of Obtaining Metaphases for Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3504-3504
Author(s):  
Kebede Hussein ◽  
Rhett P. Ketterling ◽  
Gordon W. Dewald ◽  
Rachael L. Hulshizer ◽  
Daniel G. Kuffel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Clinical Diagnosis ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Cytogenetic Study ◽  
Lymphocytic Leukemia ◽  
Myeloid Progenitor ◽  
Cytogenetic Studies ◽  
Myeloid Progenitor Cells

Abstract Background: Peripheral blood (PB) is sometimes used in place of bone marrow (BM) for cytogenetic studies during the evaluation of hematologic malignancies. We looked for clinical or laboratory features that predict success in obtaining analyzable metaphases during PB chromosome studies. Methods: The Mayo Clinic cytogenetics database was queried to identify adult cases (age > 18 years) with suspected or established hematologic neoplasm in whom PB cytogenetic studies were performed. Success defined as the acquisition of at least two metaphases, was correlated with clinical and laboratory information corresponding to the time of the PB cytogenetic study. Results: A total of 242 PB cytogenetic studies were performed: clinical diagnosis was a myeloid neoplasm in 169 patients (70%), lymphoid neoplasm in 50 (21%), and unexplained cytopenia or leukocytosis in 23 (9%). The 169 myeloid cases included 59 patients with either primary (n=39) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF) myelofibrosis (n=20), 42 with acute myeloid leukemia (AML), 15 with chronic myeloid leukemia, 9 with myelodysplastic syndrome (MDS), 8 with ET, 6 with PV, and 30 with other MPDs. The 50 lymphoid cases included 19 with chronic lymphocytic leukemia, 12 with lymphoma, 11 with acute lymphocytic leukemia (ALL), and 8 with plasma cell proliferative disorders. PB cytogenetic studies resulted in at least two analyzable metaphases (median 20, range 2–31) in 142 of the 242 study cases (59%); in univariate analysis, this was predicted by the specific clinical diagnosis (p<0.0001), presence and degree of circulating myeloid progenitor cells (p<0.0001), higher leukocyte count (p<0.001), lower platelet count (p=0.003), lower hemoglobin level (p=0.002), and presence of palpable splenomegaly (p=0.002). In multivariable analysis, only the presence of circulating myeloid progenitor cells sustained its significance and this was consistent with the high yield rates seen in PMF (80%), post-PV/ET MF (85%), AML (76%), and ALL (80%) as opposed to the low rates seen in ET (0%) and PV (2%). In 104 cases, BM cytogenetic studies were performed within one month of the PB cytogenetic studies; an abnormal BM cytogenetic finding was another independent predictor of a successful PB study (p=0.002). Conclusion: PB cytogenetic studies are most appropriate in diseases characterized by presence of circulating myeloid progenitors or blasts (e.g. PMF, AML, ALL); the yield otherwise is too small to be cost-effective. The current study also suggests a higher likelihood of a successful PB cytogenetic study in the presence of an abnormal bone marrow karyotype.

Evidence for An Anti-Cancer Barrier in a Mixed Lineage Leukemia Mouse Model in Vivo.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3347-3347
Author(s):  
Sylvia Takacova ◽  
Jiri Bartek ◽  
Lucie Piterkova ◽  
Robert K. Slany ◽  
Vladimir Divoky
Keyword(s):  
Bone Marrow ◽  
Tumor Suppressor ◽  
Mouse Model ◽  
Peripheral Blood ◽  
Myeloid Cells ◽  
Mixed Lineage Leukemia ◽  
Cell Counts ◽  
Potential Tumor Suppressor

Abstract Mixed Lineage Leukemia (MLL) mutations identify a unique group of acute leukemias with distinct biological and clinical features. Although the role of MLL in leukemogenesis has been extensively studied, a precise mechanism regarding the leukemogenic potential of MLL mutations is not known. We generated a switchable MLL-ENL-ERtm mouse model, in which the MLL-ENL oncogene has been introduced by homologous recombination and is controlled by the endogenous MLL promoter, thus, expressed at physiological levels. Due to fusion with the estrogen receptor ligand binding domain (ERtm), the MLL-ENL-ERtm protein activity is dependent on continuous provision of tamoxifen or 4-hydroxytamoxifen. The MLL-ENL-ERtm mice have developed a myeloproliferative disorder (MPD) characterized by persistent mature neutrophilia after 484,5 +/− 75,68 days of latency on a tamoxifen diet, in association with high white cell counts in peripheral blood, splenomegaly and occasionally with anemia. Blood smears showed large numbers of mature myeloid elements consisting of 40–80% neutrophils (non-segmented forms in abundance), admixed with immature myeloid elements, 3–11% monocytes and 2–6% myeloblasts. The phenotype of MPD also involved myelomonocytic proliferation with 35% immature monocytic cells in one animal and severe anemia with increased numbers of immature erythroid cells in peripheral blood in another animal. Hematoxylin- and eosin-stained sections of the bone marrow from MLL-ENL-ERtm mice revealed expansion of myeloid cell population with no signs of progressive dysplasia. We observed massive infiltration of myeloid cells (positive for myeloperoxidase) into spleen with various degree of loss of normal splenic architecture depending on disease progression. FACS profiles of both bone marrow and spleen cells showed a typical pattern of granulocyte/macrophage/monocyte surface marker expression (CD34-CD43+Mac- 1+Gr-1+CD16/32+). In vitro evaluation of hematopoetic progenitors derived from bone marrow of leukemic mice at the terminal stage of the disease revealed decreased numbers of BFU-Es and increased numbers of CFU-GMs and CFU-Gs compared to matched controls. These results correlated with the expansion of the myelomonocytic and reduction of the erythroid compartment observed in the bone marrow of these animals. The average size (cellularity) of the mutant myeloid colonies was much smaller than the colonies derived from the wild-type controls, which could be caused by a partial block of terminal differentiation of myeloid progenitors in vitro. In vivo, MLL-ENL leads to expansion of differentiated myeloid cells in our model. High penetrance and long latency of leukemia in our model permits the study of early leukemia development. Our model revealed that MLL-ENL - induced myeloproliferation occurs as early as twelve weeks after MLL-ENL-ERtm activation in the bone marrow and infiltrates the spleen with a consequent decrease in lymphoid B220+CD19+IgM+ cells. Using the TUNEL assay on bone marrow sections, we observed induction of apoptosis in the highly proliferative bone marrow compartment compared to matched controls. These results suggest activation of a potential tumor suppressor mechanism by MLL-ENL in early stages of leukemia. We are currently investigating potential tumor suppressor pathways that might be involved in MLL-ENL - induced apoptosis in preleukemia.

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