Anisocytosis Is Associated With Decreased Survival In Patients With Newly Diagnosed Myelodysplastic Syndromes: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5218-5218
Author(s):  
Ashwin Sridharan ◽  
Rishi Jain ◽  
Marcus Bachhuber ◽  
Anthony P. Lam ◽  
Yiting Yu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
High Risk ◽  
Medical Record ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Hemoglobin Concentration ◽  
Single Center ◽  
Bone Marrow Blast ◽  
High Bone

Abstract Introduction Anisocytosis is defined as excessive variation in the size of red cells. It can be quantified by measuring the red cell distribution width (RDW) and is routinely included in peripheral blood count reports. Anisocytosis has previously been associated with poorer prognosis in patients with coronary artery disease, congestive heart failure, pulmonary hypertension, pulmonary embolism, stroke, and sepsis, among other conditions. While anisocytosis is frequently present in patients with myelodysplastic syndromes (MDS), its prognostic significance is not well established. To address this, we conducted a survival analysis of patients with MDS evaluated at our clinical center. Methods To determine the association between anisocytosis and survival in patients with MDS, we conducted a retrospective cohort study. Patients with MDS evaluated at our institution between 1997 and 2011 were identified by searching medical records for ICD-9 diagnosis codes for MDS using the Clinical Looking Glass software. Patient records containing an MDS code were then examined for bone marrow biopsy results, and were included if consistent with MDS. Patient age, peripheral blood counts, cytogenetics findings, and bone marrow blast percentages at diagnosis, as well as the date of diagnosis, were abstracted from the medical record. Date of death was recorded from the medical record or by querying the Social Security Death Index. Anisocytosis was defined as an RDW ≥ 16.6%. Peripheral neutropenia was defined as an absolute neutrophil count < 800 cells/uL and a high bone marrow blast percentage as >5%. Low-risk cytogenetics was defined as either “Very Good” or “Good” by IPSS-R criteria; high-risk was either “Intermediate”, “Poor”, or “Very Poor.” We constructed Kaplan-Meier survival curves comparing those with anisocytosis to others. Survival was compared using the log-rank test. Next, we developed a Cox proportional hazards model to examine the association between anisocytosis and survival, after adjusting for age at diagnosis, hemoglobin concentration, platelet count, neutropenia, bone marrow blast percentage, and cytogenetics (values at diagnosis). Results are presented as the hazard ratio [HR] with 95% confidence interval [95% CI]. The study protocol was approved by the Montefiore Institutional Review Board. Results Of 543 patients initially identified, 30% (164/543) had bone marrow biopsies available. Of these, 84% (137/164) had cytogenetics data available. Anisocytosis at diagnosis was found in 57% (78/137). Median survival of patients with anisocytosis was 3.1 years compared to 8.5 years for those patients without anisocytosis (p = 0.02). In Cox regression analyses, anisocytosis was associated with worse prognosis (HR: 1.86 [95% CI: 1.06-3.35]). High-risk cytogenetics was significantly associated with decreased survival (HR: 3.47 [95% CI: 1.99- 5.94]). There was a trend toward a significant association between high bone marrow blast percentage and decreased survival (HR: 2.02 [95% CI: 0.96-4.01]). Age, hemoglobin concentration, platelet count, and presence of neutropenia were not significantly associated with survival. Conclusions In a single center retrospective chart review of patients with MDS, anisocytosis was associated with decreased survival when compared to patients with a normal or low RDW. This association remained in multivariable analysis adjusting for other well established prognostic variables. Our analysis was limited by a small sample size, potentially explaining the lack of significant associations found between survival and patient age, hemoglobin concentration, platelet count, and presence of neutropenia. However, it could also be possible that the effect of RDW supersedes the impact of peripheral cytopenias and even blast %, as reflected by the multivariate analysis. In conclusion, anisocytosis was significantly associated with patient prognosis and should be evaluated for for inclusion into future risk stratification systems. Disclosures: No relevant conflicts of interest to declare.

Time-to-Treatment in Chronic Myelomonocytic Leukemia - a Novel Prediction Model

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5547-5547
Author(s):  
Florian Huemer ◽  
Lukas Weiss ◽  
Viktoria Faber ◽  
Daniel Neureiter ◽  
Alexander Egle ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Lactate Dehydrogenase ◽  
High Risk ◽  
Prediction Model ◽  
Scoring System ◽  
Research Funding ◽  
Treatment Initiation ◽  
Bone Marrow Blast ◽  
Time To Treatment

Abstract Introduction For chronic myelomonocytic leukemia (CMML) several scores exist which prognosticate overall survival (OS) based on different clinical and genetic parameters. The time-to-treatment (TTT) among CMML patients is highly variable, and a predictive model to specifically estimate TTT in CMML has not been described so far. The aims of this single-center retrospective study were (a) to test and validate established myelodysplastic syndrome (MDS)-specific and CMML-specific prognostic scores in our patient cohort, (b) to evaluate which baseline factors were relevant to the time point of treatment initiation with either hydroxyurea or azacitidine, and (c) to propose a prediction model for TTT in CMML. Methods This retrospective analysis was based on the data of 55 unselected, consecutive CMML patients diagnosed and/or treated at our tertiary center between 2004 and 2015. We applied the following published prognostic models to our CMML cohort, using both OS and TTT as endpoints: the MD Anderson Prognostic Score (MDAPS), the modified MDAPS (MDAPS M1), the CMML-specific Prognostic Scoring System (CPSS), the Mayo Prognostic Model, the Düsseldorf Score, the International Prognostic Scoring System (IPSS), and the Revised International Prognostic Scoring System (IPSS-R). Results According to the CMML-specific MDAPS, 27% of our patients were classified as "higher-risk" (23% intermediate-2, 4% high-risk) (Figure 1). At the time of data analysis, 38% and 24% of patients had received azacitidine and hydroxyurea as first-line treatment. A total of 40 (73%) patients had died at the time point of data analysis. The median time of follow-up was 24.8 months (range 1.7-74.8 months). All applied MDS-specific (Düsseldorf Score, IPSS, IPSS-R) and CMML-specific (MDAPS, MDAPS M1, CPSS, Mayo Prognostic Model) prediction scores were able to significantly discriminate patient cohorts with different OS probabilities. The following variables were associated with a shorter TTT in the univariate analysis: the presence of immature myeloid cells in the peripheral blood, white blood cell count ≥14.5 G/L, platelet count <55 G/L, absolute neutrophil count ≥6 G/L, absolute lymphocyte count ≥2.3 G/L, absolute monocyte count ≥2.8 G/L, serum lactate dehydrogenase ≥223 G/L, peripheral blood blasts >0%, bone marrow blast percentage ≥7.5%, red blood cell transfusion-dependence, palpable spleen and/or symptomatic splenomegaly, and the presence of B-symptoms at the time of initial diagnosis. In multivariate analysis, the following factors remained independently associated with TTT: lactate dehydrogenase (HR 5.428; p = 0.008), bone marrow blast count (HR 4.570; p = 0.001), and platelet count (HR 2.660; p = 0.027). These three clinical parameters were included in the TTT prediction model and CMML patients were stratified into three subgroups: low-risk, intermediate-risk and high-risk. Median TTT was not reached for low-risk patients, 16.5 months for intermediate-risk patients, and almost immediate treatment initiation (0.6 months) was observed in the high-risk group (Figure 2). Conclusions We validated seven existing MDS-specific and CMML-specific prognostic scores in 55 CMML patients treated at the center in Salzburg. We were able to demonstrate that lactate dehydrogenase, bone marrow blast percentage and platelet count at initial diagnosis were the most relevant parameters for predicting time to treatment initiation in our CMML cohort. Based on these three parameters, we propose the first TTT prediction score for treatment-naïve CMML patients. Clinical implications of this score include the identification of CMML patients for early investigational trials, as well as the tailoring of individual follow-up intervals. Disclosures Huemer: Roche: Other: Travel funding; Merck: Other: Travel funding. Egle:Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: travel support; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel support. Greil:Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Eisai: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Merck: Honoraria; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; AstraZeneca: Honoraria; Roche: Honoraria, Research Funding; Sanofi Aventis: Honoraria; GSK: Research Funding; Ratiopharm: Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria. Pleyer:Celgene: Consultancy, Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria.

Microrna Expression In Patients With Myelodysplastic Syndromes Treated With Demethylating Agents

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3758-3758
Author(s):  
Meir Preis ◽  
Gregory J Tsongalis ◽  
Christopher H. Lowrey ◽  
Deborah L. Ornstein
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Mirna Expression ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Microrna Expression ◽  
Intermediate Risk ◽  
Pcr Array ◽  
Demethylating Agents

Abstract Introduction Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematopoietic stem cell disorders characterized by bone marrow failure and dysplasia of one or more blood cell lineages resulting in peripheral blood cytopenias with frequent progression to AML. Treatment with azanucleosides improves survival and quality of life without the toxicities associated with intensive chemotherapy programs. The azanucleosides are DNA demethylating agents that may improve hematopoiesis in MDS by releasing tumor suppressor genes from silencing due to promoter hypermethylation. MicroRNAs (miRNAs) play key roles in cell growth and differentiation and oncogenic transformation. Dysregulation of miRNA expression may contribute to the development of MDS, as expression of several miRNAs has been reported to be downregulated in bone marrow cells from MDS patients. We performed the current study to test the hypothesis that treatment with demethylating agents modulates miRNA expression in hematopoietic tissue from MDS patients and to characterize the specific changes in miRNA expression. Methods This was a two-center, prospective cohort study to evaluate miRNA expression signatures in hematopoietic progenitor cells isolated from the bone marrow of subjects undergoing evaluation for peripheral blood cytopenias. Subjects were included for analysis if RNA of sufficient quality was available and the final pathologic diagnosis was one of the following: 1) normal (served as controls), 2) dyspoiesis without meeting criteria for MDS and without cytogenetic abnormalities, 3) MDS and 4) acute myeloid leukemia (AML) with myelodysplasia-related changes. Subjects who underwent treatment with a demethylating agent had bone marrow collected after treatment for before and after comparisons of miRNA signatures. Mononuclear cells were isolated from bone marrow aspirate specimens by density gradient centrifugation using a Ficoll-Paque technique. MicroRNA was isolated using the miRNeasy kit (Qiagen) and was analyzed using miScript miRNA PCR Array Human Cell Development & Differentiation (MIHS-103Z, Qiagen). Isolated microRNA was checked for quality control using miScript miRNA QC PCR array. Data were analyzed using Qiagen analysis software for microRNA, and miRNA levels are expressed as 2-ΔΔCT. P-values<0.05 were considered statistically significant. Results Forty subjects were enrolled in the study. Eight subjects were excluded after the initial bone marrow biopsy for poor quality RNA (n = 3) or inappropriate diagnoses (lymphoid (n = 3) or myeloproliferative (n = 2) neoplasms). The remaining 32 subjects comprised 5 groups: 1) normal (n = 6), 2) dyspoiesis but not meeting criteria for MDS and normal cytogenetics (n = 5), 3) low-intermediate risk MDS (n = 8), 4) high-risk MDS (n = 6) and 5) AML with myelodysplasia-related changes (n = 7). Bone marrow samples were obtained from 5 patients after treatment with azanucleosides. The miRNA expression pattern in subjects with normal bone marrow and in those with no clear morphological evidence of MDS (groups 1 & 2) was similar. Conversely, subjects with low-intermediate risk MDS showed decreased expression of multiple miRNAs compared to controls (> 2 fold decrease in 22/84 miRNAs), most notably miR-126-3p (p = 0.02) and miR-20a-5p (p = 0.04). In contrast, high-risk MDS patients demonstrated a significant overall increase in microRNA expression (>2-fold increase in 33/84 miRNAs), especially miR-20b-5p (p = 0.04) and miR-125b-5p (p = 0.01). Treatment with demethylating agents led to decreased expression of most miRNAs (>2-fold decrease in 14/84 miRNAs), including miR-181a and let-7a, but an increase in others, such as miR-22 (2.3-fold increase). We obtained similar results in experiments conducted with primary bone marrow samples that were treated with demethylating agents ex vivo. Summary Our study is the first to characterize the changes in miRNA expression patterns in patients with MDS treated with demethylating agents. We also identify novel miRNA candidates to be further evaluated as biomarkers for assessing response to treatment with demethylating agents (e.g., miR-22, which has been described as possibly having a role in regulating TET2). We also demonstrate the striking difference in the pattern of miRNA expression between low-risk and high-risk MDS patients, a feature that may one day be exploited to assist with making treatment decisions. Disclosures: No relevant conflicts of interest to declare.

Increased Expression of Circulating Mir-22 in the Peripheral Blood of Patients with Myelodysplastic Syndromes Was Associated with Poorer Prognosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2854-2854
Author(s):  
Yuesheng Meng ◽  
Fanli Hua ◽  
Ying Li ◽  
Song Gao
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Expression Levels ◽  
Healthy Donors ◽  
Chi Square Analysis

Abstract The molecular pathogenesis of myelodysplastic syndromes (MDS) has not been completely elucidated. Deregulation of expression of some microRNA has been implicated in hematological disorders including MDS. An oncogenic role for miR-22 was recently suggested in MDS in which the expression of miR-22 was increased. However, there were corroborations showing that it could be a tumor suppressor in acute myeloid leukemia. In this study, we examined the expression levels of circulating miR-22 in the plasma of patients with MDS and evaluated its significance in clinical context. The diagnosis of MDS was made according to the WHO classifications and subtypes included 8 cases of RA, 14 cases of RCMD and 6 cases of RARS/RCMD-RS, 10 cases RAEB1 and 7 cases RAEB2. Twenty cases of healthy donors were enrolled as normal control. Written informed consent for sample collection was obtained from all subjects enrolled. EDTA-anticoagulated peripheral blood samples were collected and centrifuged. Circulating microRNAs were purified from the plasma with miRNeasy serum kit (Qiagen). Expression of miR-22 was reverse- transcripted and measured with stem-loop real time quantitative polymerase chain reaction assay. First of all, we proved that the expression of miR-22 was detectable in the plasma of patients with MDS as well as of healthy donors. Our result showed that the expression levels of circulating miR-22 in MDS patients were higher than that in healthy donors (medians 1.360 vs 1.000, P<0.05), among which 13 patients (37.1%) showed marked increase of miR-22 expression (>2 times). Due to the high heterogeneity of MDS and relatively smaller sample size, the subtypes were grouped into two major categories based on IPSS: the low-risk group (including RA, RCMD and RARS/RCMD-RS, totally 18 cases) and the high-risk group (RAEB1 and RAEB2, 17 cases in total). Relative levels of circulating miR-22 were higher in the high-risk group than in the low-risk group (medians= 1.081 vs 2.317, P<0.05). A follow-up study revealed an association of the expression levels of miR-22 with prognosis. Patients with increased expression of miR-22 had poorer clinical response (Chi-square analysis, P<0.05) and lower overall survival rate (Kaplan-Meier analysis, P<0.05). We compared the levels of miR-22 in the plasma with that of mononuclear cells of bone marrow in some MDS patients and found that the relative levels of miR-22 in the plasma and bone marrow cells were not directly co-related (P>0.05), indicating it could be an independent prognostic factor. In summary, this study confirmed an oncogenic presence of miR-22 in MDS. Given the fact that there is a lack of blastic cells in the bone marrow of patients with low-risk MDS but their plasma or serum is easy to obtain, the detection of circulating miR-22 may be of value as a molecular marker in the prognosis of MDS. Disclosures No relevant conflicts of interest to declare.

Myelodysplastic syndromes/myeloproliferative overlap neoplasms

2020 ◽  
pp. 191-203
Author(s):  
Eric Padron ◽  
Tariq I. Mughal ◽  
David Sallman ◽  
Alan F. List
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Stem Cell ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Myeloproliferative Neoplasms ◽  
Bone Marrow Failure ◽  
Disease Outcomes ◽  
Genomic Landscape ◽  
Bone Marrow Dysplasia

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are haematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) that display a paradoxical bone marrow phenotype hallmarked by myeloid proliferation in the context of bone marrow dysplasia and ineffective haematopoiesis. The unfolding MDS/MPN genomic landscape has revealed numerous mutations in signalling genes, such as CBL, JAK2, NRAS, KRAS, CSF3R, and others involving the spliceosome complex. These observations suggest that comutation of genes involved in dysplasia and bone marrow failure along with those of cytokine receptor signalling may, in part, explain the dual MDS/MPN phenotype. The respective MDS/MPN diseases are identified by the type of myeloid subset which predominates in the peripheral blood. Currently there are no standard treatment recommendations for most patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic endpoints and standardized response criteria for clinical trials.

scholarly journals Detection of chromosome 20q deletions in bone marrow metaphases but not peripheral blood granulocytes in patients with myeloproliferative disorders or myelodysplastic syndromes

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1561-1570 ◽  
Author(s):  
FA Asimakopoulos ◽  
TL Holloway ◽  
EP Nacheva ◽  
MA Scott ◽  
P Fenaux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Myeloproliferative Disorders ◽  
Pcr Analysis ◽  
Multipotent Progenitors ◽  
The Common ◽  
Polymerase Chain ◽  
A Minor

Myeloproliferative disorders and myelodysplastic syndromes arise in multipotent progenitors and may be associated with chromosomal deletions that can be detected in peripheral blood granulocytes. We present here seven patients with myeloproliferative disorders or myelodysplastic syndromes in whom a deletion of the long arm of chromosome 20 was detectable by G-banding and/or fluorescence in situ hybridization in most or all bone marrow metaphases. However, in each case, microsatellite polymerase chain reaction (PCR) using 15 primer pairs spanning the common deleted region on 20q showed that the deletion was absent from most peripheral blood granulocytes. The human androgen receptor clonality assay was used to show that the vast majority of peripheral blood granulocytes were clonal in all four female patients. This represents the first demonstration that the 20q deletion can arise as a second event in patients with pre-existing clonal granulopoiesis. Microsatellite PCR analysis of whole bone marrow from two patients was consistent with cytogenetic studies, a result that suggests that cytogenetic analysis was not merely selecting for a minor subclone of cells carrying the deletion. Furthermore, in one patient, the deletion was present in both erythroid and granulocyte/monocyte colonies. This implies that the absence of the deletion in most peripheral blood granulocytes did not reflect lineage restriction of the progenitors carrying the deletion but may instead result from other selective influences such as preferential retention/destruction within the bone marrow of granulocytes carrying the deletion.

scholarly journals Evidence for a Vessel Wall Defect in Immuno-thrombocytopenic Hamsters

Blood ◽  
1960 ◽  
Vol 15 (5) ◽  
pp. 675-680 ◽  
Author(s):  
RAJENDRA G. DESAI ◽  
GEORGE P. FULTON
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Negative Pressure ◽  
Peripheral Blood ◽  
Vessel Wall ◽  
Bleeding Time ◽  
Red Cell ◽  
Clot Retraction ◽  
Wall Defect ◽  
Pressure Tests

Abstract Experimental purpura was produced in the hamster by administration of anti-platelet serum obtained from rabbits previously injected with hamster platelets. Spontaneous petechiae and generalized bleeding were observed. The derangement in the hemostatic mechanism has been analyzed by study of the changes in blood, bone marrow and vessel walls. The platelet count in peripheral blood fell from 9.02 ± 0.85 (x 105) to 0.66 ± 0.32 (x 105) at 24 hours after 2.0 ml. intravenous injection of antiplatelet serum. The red cell and hemoglobin values dropped to 50 per cent before death related to generalized bleeding occurred. Significant changes were seen in the megakaryocytes of the bone marrow. The bleeding time and clot retraction were extended. Evidence for a defect in the vessel wall has been shown by the microelectrode, moccasin snake venom and negative pressure tests. The cause of bleeding has been postulated as a double defect resulting from a decrease of platelets in the circulation and an alteration in the integrity of the vessel wall or perivascular supporting sheath.

scholarly journals Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3660-3667 ◽  
Author(s):  
M Delforge ◽  
H Demuynck ◽  
P Vandenberghe ◽  
G Verhoef ◽  
P Zachee ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Allogeneic Bone Marrow Transplantation ◽  
High Dose ◽  
Allogeneic Bone ◽  
Hematopoietic Progenitors ◽  
Daughter Cells ◽  
Mobilized Peripheral Blood

Myelodysplastic syndromes (MDS) form a heterogeneous group of clonal hematopoietic disorders with unfavourable prognosis. Allogeneic bone marrow transplantation is the only potentially curative treatment, but remains limited to a small subgroup of younger patients with HLA- compatible donors. As autologous stem cell transplantation is currently being explored as an alternative treatment strategy for MDS, more information needs to be acquired regarding the clonal nature of the progenitor cells in these autografts. Therefore, we have analyzed the clonal patterns of highly purified hematopoietic progenitors and their mature daughter cells in mobilized peripheral blood collections produced from five female patients with high-risk MDS in complete hematologic remission. X-chromosome activation patterns of flow-sorted immature (CD34 + 38low, CD34 + 33low) and committed (CD34 + 38high, CD34 + 33high) progenitors were studied with the polymerase chain reaction-based HUMARA assay. In four patients, a polyclonal remission was shown in all stem cell subpopulations and their mature daughter cells whereas one patient was found to remain skewed in all fractions, except T lymphocytes. This study provides strong evidence that polyclonal immature hematopoietic progenitors can be mobilized and harvested in patients high-risk MDS after treatment with high-dose chemotherapy.

Over-Expression of Cancerous Inhibitor of PP2A (CIP2A) in Bone Marrow Cells from Patients with a Group of High-Risk Myelodysplastic Syndromes

2013 ◽  
Vol 20 (2) ◽  
pp. 399-407 ◽  
Author(s):  
Na Li ◽  
Shinya Abe ◽  
Morito Kurata ◽  
Shiho Abe-Suzuki ◽  
Iichiroh Onishi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Over Expression ◽  
Marrow Cells
Sign in / Sign up

Export Citation Format

Share Document