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Florid plasmacytosis in a case of acute myeloid leukemia: A diagnostic dilemma  [cached]
Rangan Aruna,Arora Bhavna,Rangan Pooja,Dadu Tina
Indian Journal of Medical and Paediatric Oncology , 2010,
Abstract: The association of acute myeloid leukemia (AML) with plasmacytosis is a known, although rare event. There are very few case reports documenting an increase in the number of plasma cells at the time of AML diagnosis. Here, we present the case of a 65-year-old male diagnosed as acute myelomonocytic leukemia with exuberant plasmacytosis, which posed a difficulty in diagnosis. Paracrine interleukin-6 production by leukemic blast cells is thought to contribute to this associated reactive plasma cell proliferation.
Isolated granulocytic sarcoma of the pancreas: A tricky diagnostic for primary pancreatic extramedullary acute myeloid leukemia
Mathieu Messager, David Amielh, Caroline Chevallier, Christophe Mariette
World Journal of Surgical Oncology , 2012, DOI: 10.1186/1477-7819-10-13
Abstract: Granulocytic sarcoma (GS) is an extramedullary solid tumor mass composed of immature myeloid cells [1]. GS is a rare manifestation of acute myeloid leukemia (AML) usually arising during or after the course of the disease, in up to 8% of patients in autopsy studies [2]. Occasionally, it can be the first and the only manifestation of AML, leading to diagnostic challenges. We report two exceptional cases of isolated pancreatic GS to focus physicians' attention to specific diagnostic and therapeutic strategies for a solid pancreatic mass.The first patient was a 45-year-old woman, without significant comorbidity, who was referred to our institution for surgery. Epigastric pain with jaundice began one month previously without performance status alteration. Standard blood exams exhibited cholestasis (alkaline phosphatases 3.8 N, gama-glutamyl transpeptidases 37 N) and hyperamylasemia (1.9 N) with normal values of hemoglobin, white blood cells, platelets, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). Abdominal computed tomodensitometry (CT scan), magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) of the pancreas all identified the distension of both the common bile duct (15 mm) and the Wirsung duct (6 mm), above a 28 × 20 mm irregular, hypoechoic and hypodense mass of the pancreatic head, without any lymph node or vascular invasion or distant secondary lesion detected. Based on the symptoms, a suspected diagnosis of pancreatic adenocarcinoma and a resectable mass, it was determined to proceed with primary surgery without obtaining preoperative sample biopsies. Curative whipple pancreaticoduodenectomy with regional lymphadenectomy was performed with no specific peroperative discovery and uneventful postoperative course. Histological examination of the surgical specimen revealed a pancreatic GS based on the presence of cells of myeloid lineage with positive immunostaining for CD43 myeloid-associated antigen (Figure 1A), whereas immu
Optimization of the indications for allogeneic stem cell transplantation in Acute Myeloid Leukemia based on interactive diagnostic strategies
Hartwig M,Zander AR,Haferlach T,Fehse B
Cellular Therapy and Transplantation , 2008,
Abstract: The indications for allogeneic stem cell transplantation (SCT) in Acute Myeloid Leukemia (AML) represent a real challenge due to the clinical and genetic heterogeneity of the disorder. Therefore, an optimized indication for SCT in AML first requires the determination of the individual relapse risk based on diverse chromosomal and molecular prognosis-defining aberrations. A broad panel of diagnostic methods is needed to allow such subclassification and prognostic stratification: cytomorphology, cytogenetics, molecular genetics, and immunophenotyping by multiparameter flow cytometry. These methods should not be seen as isolated techniques but as parts of an integral network with hierarchies and interactions. Examples for a poor risk constellation as a clear indication for allogeneic SCT are provided by anomalies of chromosome 7, complex aberrations, or FLT3-length mutations. In contrast, the favorable reciprocal translocations such as the t(15;17)/PML-RARA or t(8;21)/AML1-ETO are not indications for SCT in first remission due to the rather good prognosis after standard therapy. Further, the indication for SCT should include the results of minimal residual disease (MRD) diagnostics by polymerase chain reaction (PCR) or flow cytometry. New aspects for a safe and fast risk stratification as basis for an optimized indication for SCT in AML might be provided by novel technologies such as microarray-based gene expression profiling.
Usefulness of Presepsin (Soluble CD14 Subtype) as a Diagnostic Marker of Sepsis in Egyptian Patients with Acute Myeloid Leukemia  [PDF]
Maged Maurice, Dalia Nafea, Mohamed El Sawy, Rania Soelam, Sylvia Youssef
American Journal of Molecular Biology (AJMB) , 2014, DOI: 10.4236/ajmb.2014.44019
Abstract: Background: Systemic inflammatory response syndrome (SIRS) is a systemic inflammatory response to a variety of insults. Presepsin; the soluble CD14 subtype is a novel soluble CD14 molecule that is useful for diagnosing sepsis. It plays an important role in modulating the immune response to endotoxin in vitro and vivo. The aim: Of the study was to evaluate the usefulness of presepsin as a diagnostic marker of sepsis in acute leukemia. Methods: The current study was carried out on 40 adult patients with acute myeloid leukemia after receiving chemotherapy. 10 clinically normal individuals were included in the study to measure the level of presepsin. Results: This study was conducted on 50 individuals divided into 2 groups. Group I included 40 adult AML patients who fulfilled at least two of the diagnostic criteria for SIRS and Group II were 10 healthy adult persons as a control group. In Group I there were 11 patients (27.5%) having SIRS, 8 (20%) having sepsis, 9 (22.5%) having severe sepsis and 12 (30%) having septic shock. Data indicate that presepsin level was significantly higher in patients than control P = 0.017. Our results showed that the level of presepsin has a significantly positive correlation to the degree of severity of sepsis with P value 0.0001. Using the ROC curve, we found that presepsin was more specific than CRP in detection of sepsis. Conclusion: sCD14-ST (presepsin) is a new important marker for diagnosis and prognosis of sepsis. Its level increases in the first six hours after the onset of sepsis. Our data demonstrated that the concentration of presepsin is specifically increased during sepsis and is directly proportional to the degree of sepsis. Regarding sensitivity and specificity of presepsin in the discrimination of sepsis patients from healthy controls, a high specificity but low sensitivity was reported by most of the studies.
Diagnostic and prognostic value of plasma level of microRNA-92a in acute myeloid leukemia  [PDF]
Nabil El-Halawani, Nahla Hamed, Mohamed Eldafrawi, Zeinab Mourad, Amani Sorour, Omar Ghallab
American Journal of Molecular Biology (AJMB) , 2014, DOI: 10.4236/ajmb.2014.41001

Background: MicroRNAs (miRNAs) are short noncoding RNAs of ~21 to 23 nucleotides in length that post-transcriptionally regulate mRNA expression. Highthroughput methodologies have shown deregulated miRNA expression in an increasing number of human cancers. MiRNA expression patterns have been found to distinguish tumors of different developmental origin, even better than traditional mRNA expression profiling. Aim: To assess the plasma level of microRNA-92a in adult acute myeloid leukemia and to correlate it with prognostic factors and therapeutic response. Patients and Methods: This study was carried out on fifty AML patients as well as fifty healthy subjects as control. Conventional cytogenetics was performed on patients group only while measurement of the plasma level of miRNA-92a using TaqMan quantitative RT-PCR with miRNA-638 as endogenous reference for standardization and FLT3/ITD mutation was performed on patients and controls. Results: The differences in the ratio or relative quantitation (RQ) of plasma miRNa-92a to miRNA-638 in patients group to the control group have confirmed statistical significance. Also there was significant negative correlation between RQ of miRNA-92a and white blood count in patient group. Patients who achieved a response after induction chemotherapy had a mean RQ of miRNA-92a higher than non-responder with statistical significance. With regard to cytogenetics, favorable risk cytogenetics had meant RQ of miRNA-92a that was comparable to intermediate risk cytogenetics. While poor risk cytogenetics had a mean RQ which is significantly lower than both favorable and intermediate risk cytogenetics. Summary/Conclusions: Our data suggest the potential importance of the microRNA-92a as noninvasive cancer biomarkers helping in diagnosis, clinical prediction and therapeutic response.

Recurrence of a t(8;21)-Positive Acute Myeloid Leukemia in the Form of a Granulocytic Sarcoma Involving Cranial Bones: A Diagnostic and Therapeutic Challenge  [PDF]
Ambra Di Veroli,Alessandro Micarelli,Mariagiovanna Cefalo,Eleonora Ceresoli,Daniela Nasso,Laura Cicconi,Simone Mauramati,Fabrizio Ottaviani,Adriano Venditti,Sergio Amadori
Case Reports in Hematology , 2013, DOI: 10.1155/2013/245395
Abstract: Granulocytic sarcoma (GS) is a rare extramedullary solid tumor defined as an accumulation of myeloblasts or immature myeloid cells. It can cooccur with or precede the acute myeloid leukemia (AML) as well as following treated AML. The incidence of GS in AML patients is 3–8% but it significantly rises in M2 FAB subtype AML. This variety of AML harbors t(8;21) in up to 20–25% of cases (especially in children and black ones of African origin) and, at a molecular level, it is characterized by the generation of a fusion gene known as RUNX1-RUNX1T1. Approximately 10% of M2 AML patients will develop GS, as a consequence, the t(8;21) and the relative transcript represent the most common cytogenetic and molecular abnormalities in GS. FLT3-ITD mutation was rarely described in AML patients presenting with GS. FLT3 ITD is generally strongly associated with poor prognosis in AML, and is rarely reported in patients with t(8;21). GS presentation is extremely variable depending on organs involved; in general, cranial bones and sinus are very rarely affected sites. We report a rare case of GS occurring as a recurrence of a previously treated t(8;21), FLT3-ITD positive AML, involving mastoid bones and paravertebral tissues. 1. Introduction Granulocytic sarcoma (GS) is a rare extramedullary solid tumor defined according to the 2008 WHO classification as an accumulation of myeloblasts or immature myeloid cells. It can cooccur with acute myeloid leukemia (AML) or precede its diagnosis as well as following previously treated AML as extramedullary isolated manifestation of relapse [1, 2]. The incidence of GS in AML patients is about 3–8%, but it significantly rises in patients diagnosed with an M2 FAB subtype AML. This variety of AML harbors a translocation t(8;21) in up to 20–25% of cases [3]. At a molecular level, such translocation is characterized by the generation of a fusion gene known as RUNX1-RUNX1T1. Approximately 10% of M2 AML patients will develop GS, as a consequence, the t(8;21) and the relative transcript RUNX1-RUNX1T1 represent the most common cytogenetic and molecular abnormalities seen in GS [4]. Rarely, it was described the presence of FLT3 internal tandem duplication (ITD) mutation in AML patients presenting with GS. FLT3 ITD is generally strongly associated with poor prognosis in AML and is rarely reported in patients with t(8;21) [5–7]. GS is more frequently reported in children, with black ones of African origin having a significantly higher incidence particularly in association with t(8;21) [8, 9]. GS clinical presentation is extremely variable depending
Clinical proteomics of myeloid leukemia
Sigrun M Hjelle, Rakel B Forthun, Ingvild Haaland, H?kon Reikvam, Gry Sj?holt, ?ystein Bruserud, Bj?rn T Gjertsen
Genome Medicine , 2010, DOI: 10.1186/gm162
Abstract: Myeloid leukemia is the result of uncontrolled clonal proliferation in the erythroid, monocytic and granulocyte lineages and their precursors, originating from hematopoietic stem cells of the bone marrow (Figure 1). It can be roughly divided into acute and chronic disease, reflecting disease development and survival if untreated (Table 1), but the World Health Organization classification of the various subsets of acute and chronic leukemia is increasingly dependent on molecular diagnostics because of the wider use of targeted therapy.Myeloid leukemia frequently involves mutations of signal transduction pathways, including mutations of the tyrosine-specific protein kinase Janus kinase 2 (JAK2) in erythroid neoplasia, the pathognomonic BCR-ABL (breakpoint cluster region-Abelson) kinase gene translocation in chronic myeloid leukemia (CML), and FMS-like tyrosine kinase 3 (FLT3) gene mutation in acute myeloid leukemia (AML) [1,2]. All of these mutations are proposed to activate signal transduction pathways, which either belong to the wild-type kinase counterpart or, in the case of FLT3 mutation of the juxta membranous region, activate parallel signal transduction pathways that are not activated by ligand-stimulated wild-type FLT3. In AML, the FLT3 gene is mutated in more than 25% of patients, but inhibitors of FLT3 have so far not been proven to enhance overall survival.The fact that the BCR-ABL gene chimera in CML is drug-able has revolutionized the treatment of this serious disease. Overall 5-year survival in the pre-tyrosine kinase inhibitor (TKI) era was approximately 50%, compared with over 80% survival at 6 years in patients treated with imatinib [3]. Patients usually experience tolerable side-effects that predominantly reflect the off-targets of imatinib, for example, platelet-derived growth factor receptor inhibition leading to edema. A chemical proteomic approach [4] has identified new protein targets for imatinib, and a similar strategy has recently been used f
Seroprevalence and epidemiological correlates of Toxoplasma gondii infections among patients referred for hospital-based serological testing in Doha, Qatar
Marawan A Abu-Madi, Naema Al-Molawi, Jerzy M Behnke
Parasites & Vectors , 2008, DOI: 10.1186/1756-3305-1-39
Abstract: We analysed the serological response to Toxoplasma gondii of 1625 subjects referred for routine hospital based serological tests in Doha, Qatar. Prevalence of current/recent infection was assessed through an enzyme-linked immunosorbent assay (ELISA) for the presence of specific anti-T. gondii IgM antibodies, and previous history of infection through IgG.Overall prevalence of IgG responses was 29.8% and this did not differ between the sexes nor between the three years of the study although there was a marked age effect. Among children less than 1 year old prevalence was 22.9%, but then dropped to <4% in the 1 year old group, indicating that these antibodies were most likely acquired in utero from immune mothers. Prevalence then increased steadily to peak at 41.2% among the oldest age class (>45 years). The prevalence of IgG antibody also varied significantly with region of origin, with higher rates for subjects from Africa, followed by those from the Eastern Mediterranean or Asia and lowest rates for subjects from the Arabian Peninsula. No IgM antibodies were detected in any subjects younger than 19 years, but prevalence increased to plateau at 7 – 9% in subjects aged over 20 years, and also varied with region of origin. In this case prevalence was highest among subjects from the Arabian Peninsula and least among those from Asia. Prevalence of IgM was higher among male subjects but did not vary between the three years of the study.Although these data are based on a selected subset of the population, they nevertheless provide the first evidence that toxoplasmosis is endemic in Qatar in the human population, and that both age and region of origin play a role in the epidemiology of the infection. Concerns relating to the role of high density of feral cats in sustaining the infection were highlighted.Toxoplasmosis is a cosmopolitan disease arising from infection with the cat-borne Apicomplexan, coccidian protozoan Toxoplasma gondii, an obligate intracellular parasite tha
The Possible Diagnostic and Prognostic Use of Systemic Chemokine Profiles in Clinical Medicine—The Experience in Acute Myeloid Leukemia from Disease Development and Diagnosis via Conventional Chemotherapy to Allogeneic Stem Cell Transplantation  [PDF]
H?kon Reikvam,Hanne Fredly,Astrid Olsnes Kittang,?ystein Bruserud
Toxins , 2013, DOI: 10.3390/toxins5020336
Abstract: Chemokines are important regulators of many different biological processes, including (i) inflammation with activation and local recruitment of immunocompetent cells; (ii) angiogenesis as a part of inflammation or carcinogenesis; and (iii) as a bridge between the coagulation system and inflammation/immune activation. The systemic levels of various chemokines may therefore reflect local disease processes, and such variations may thereby be used in the routine clinical handling of patients. The experience from patients with myeloproliferative diseases, and especially patients with acute myeloid leukemia (AML), suggests that systemic plasma/serum cytokine profiles can be useful, both as a diagnostic tool and for prognostication of patients. However, cytokines/chemokines are released by a wide range of cells and are involved in a wide range of biological processes; the altered levels may therefore mainly reflect the strength and nature of the biological processes, and the optimal clinical use of chemokine/cytokine analyses may therefore require combination with organ-specific biomarkers. Chemokine levels are also altered by clinical procedures, therapeutic interventions and the general status of the patients. A careful standardization of sample collection is therefore important, and the interpretation of the observations will require that the overall clinical context is considered. Despite these limitations, we conclude that analysis of systemic chemokine/cytokine profiles can reflect important clinical characteristics and, therefore, is an important scientific tool that can be used as a part of future clinical studies to identify clinically relevant biomarkers.
Diagnostic value of pleural fluid interferon-gamma and adenosine deaminase in patients with pleural tuberculosis in Qatar
Khan FY, Hamza M, Omran AH, Saleh M, Lingawi M, Alnaqdy A, Abdel Rahman MO, Ahmedullah HS, Hamza A, Ani AA, Errayes M, Almaslamani M, Mahmood AA
International Journal of General Medicine , 2013, DOI: http://dx.doi.org/10.2147/IJGM.S39345
Abstract: gnostic value of pleural fluid interferon-gamma and adenosine deaminase in patients with pleural tuberculosis in Qatar Original Research (671) Total Article Views Authors: Khan FY, Hamza M, Omran AH, Saleh M, Lingawi M, Alnaqdy A, Abdel Rahman MO, Ahmedullah HS, Hamza A, Ani AA, Errayes M, Almaslamani M, Mahmood AA Published Date January 2013 Volume 2013:6 Pages 13 - 18 DOI: http://dx.doi.org/10.2147/IJGM.S39345 Received: 18 October 2012 Accepted: 06 December 2012 Published: 10 January 2013 Fahmi Yousef Khan,1 Maha Hamza,2 Aisha Hussein Omran,2 Muhannad Saleh,2 Mona Lingawi,2 Adel Alnaqdy,3 Mohamed Osman Abdel Rahman,3 Hasan Syed Ahmedullah,4 Alan Hamza,1 Ahmed AL Ani,1 Mehdi Errayes,1 Mona Almaslamani,4 Ahmed Ali Mahmood2 1Department of Medicine, 2Department of Pulmonary Medicine, 3Laboratory Department, 4Infectious Disease Division, Department of Medicine, Hamad General Hospital, Doha, Qatar Objective: To investigate the diagnostic utility of interferon-gamma (IFN-γ) and adenosine deaminase (ADA) in tuberculous pleural effusions by determining the best cutoff levels of these two markers for pleural tuberculosis, in the context of the local epidemiological settings in Qatar. Methods: We prospectively studied IFN-γ and ADA levels in the pleural fluid of patients presenting to Hamad General Hospital between June 1, 2009 and May 31, 2010. Results: We studied 103 patients with pleural effusions, 72 (69.9%) with pleural tuberculosis, and 31 (30.1%) with nontuberculous etiologies. The mean IFN-γ concentration for the group with tuberculous effusions was significantly higher than that in the group with nontuberculous effusions (1.98 ± 81 vs 0.26 ± 10 pg/mL [P < 0.0001]). The mean ADA activity for the tuberculous effusions group was significantly higher than that in group with nontuberculous effusions (41.30 ± 20.09 vs 14.93 ± 14.87 U/L [P < 0.0001]). By analysis of receiver operating characteristic (ROC) curves, the best cutoff values for IFN-γ and ADA were 0.5 pg/mL and 16.65 U/L, respectively. The results for IFN-γ vs ADA were: for sensitivity, 100% vs 86%, respectively; for specificity, 100% vs 74%, respectively; for positive predictive value, 100% vs 88.5%, respectively; and for negative predictive value, 100% vs 69.7%, respectively. Conclusion: IFN-γ and ADA could be used as valuable parameters for the differentiation of tuberculous from nontuberculous effusion, and IFN-γ was more sensitive and specific for tuberculous effusion than ADA.
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