scholarly journals Association of HLA -A, -B and -DRB1 alleles with hematological diseases in Vojvodina

Genetika ◽  
2013 ◽  
Vol 45 (1) ◽  
pp. 63-74
Author(s):  
Svetlana Vojvodic ◽  
Dusica Ademovic-Sazdanic ◽  
Ivan Busarcevic
Keyword(s):  
Lymphoblastic Leukemia ◽  
Polymerase Chain Reaction Analysis ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Hla Typing ◽  
Hematological Diseases ◽  
Mhc Genes ◽  
Predisposing Genes ◽  
Acute Nonlymphoblastic Leukemia ◽  
Preventive Fraction

Major histocompatibility complex (MHC) genes are involved in various mechanisms of pathogenesis and immunoediting of hematological diseases. This study aimed to investigate the association between HLA -A, -B and -DRB1 alleles with hematological diseases. In this study, we performed DNA-based HLA typing by polymerase chain reaction analysis with sequence-specific primers (PCR-SSP) to distinguish HLA-A, -B, and -DRB1 alleles. Eighty-two patients with hematological diseases (29 with acute lymphoblastic leukemia (ALL), 19 with acute nonlymphoblastic leukemia (ANLL), 5 with chronic myelogenous leukemia (CML), 2 with chronic lymphocytic leukemia (CLL), 9 with myelodysplastic syndrome (MDS), 9 with lymphomas (M.Hodgkin (HL) and non-Hodgkin (NHL)), 7 with aplastic anemia (AA) and 2 with multiple myeloma (MM)), were included in the study and compared with 111 healthy blood donors, residents from Vojvodina, evaluating the strength of the observed associations by measuring the aetiologic and preventive fractions. Among the alleles significantly associated with hematological diseases, HLA-A*24 showed an aetiologic fraction higher than those of HLA-A*26 and A*25 (RR=1.027, EF=1.233, RR=1.047, EF=1.141 and RR=1.213, EF=0.910).Negative association with significant preventive fraction was observed with HLA-B*18 and HLA-DRB1*11 alleles, with RR=0.400, PF=0.179 and RR=0.587, PF=0.176. Our results suggest that HLA-A*24, A*26 and A*25 as associated more frequently than other specificities with a hypothetical disease predisposing genes, may play a role in the pathogenesis of hematological diseases.

BONE MARROW PROFILE IN HEMATOLOGICAL DISORDERS IN YEMENI PATIENS

2021 ◽  
pp. 61-65
Author(s):  
Saeed Thabet Nasher ◽  
Fayed Alyousufy ◽  
Khaled Alkubati ◽  
Sadam Al Halimy ◽  
Ramia Al Athwary
Keyword(s):  
Bone Marrow ◽  
Visceral Leishmaniasis ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Examination ◽  
Myeloproliferative Disorder ◽  
Lymphocytic Leukemia ◽  
Published Data ◽  
Hematological Disorders ◽  
Hematological Diseases ◽  
Age Related

There is paucity of information about the prevalence of hematological disorders in Yemen and neighboring countries .This is the rst project to evaluate the relative spectrum of hematological diseases in Taiz and Ibb governorate Yemen ,by method of bone marrow examination which is considered an important valuable diagnostic tool, for evaluation and nal diagnosis of various hematological and non-hematological disorders especially when CBC and peripheral blood lm study and other investigation failed to give a diagnosis . OBJECTIVES: The aim of this study was to evaluate the spectrum of haematological diseases diagnosed by bone marrow examination in Taiz and IBB governorates Yemen between September 2016 and October 2020 .Patients and method : A total of 1108 patients aged between (1 -100 )years old were evaluated by bone marrow examination at referral hematological center in IBB city Yemen . Relevant investigations were performed when needed. After exclusion of 98 patients with normal bone marrow ndings ,a total of 1010 patients had hematological disorders , and their data were analyzed. There were 527 (52.2 %) males and 483(47.8 %) females . A total of 655(64.9%) patients had benign hematological diseases and 355 (35.1% ) patients had malignant hematological diseases . RESULTS :A total of 138 patients had Iron deciency anemia ,107 had immune thrombocytopenic purpura (ITP) , 92 had hypersplenism,84 had Acute lymphoblastic leukemia ,79 had Acute myeloid leukaemia, 71 had megaloblastic anemia 58 had myeloproliferative disorder , 53 had Chronic myeloid leukemia , 45 had hemolytic anemia ,45had visceral leishmaniasis. 44 had malaria, 38 had chronic lymphocytic leukemia 38 had anemia of chronic disease ,25 had aplastic anemia ,25 had myelodysplastic syndromes, ,21 had anemia of infection ,19 had congenital syndroms,7had multiple myeloma ,6 had mixed deciency anemia and 5 had metastatic deposits , 4 had myeloid leukomoid reaction ,4 had lymphoma inltration and 2 had hairy cell leukemia . Sex- and age-related distribution of the various disorders was also presented. CONCLUSION: The anemias of all types were the most frequently encountered diagnosis followed by acute and chronic leukemias , ITP , Hypersplenism , ,myeloproliferative disorder , visceral leishmaniasis , malaria, myelodysplastic syndrome and congenital syndromes respectively. The other haematological disorders were less common. These ndings are comparable with published data in previous studies done in Yemen and other developing countries

Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene

1991 ◽  
Vol 11 (9) ◽  
pp. 4710-4716
Author(s):  
M Kelliher ◽  
A Knott ◽  
J McLaughlin ◽  
O N Witte ◽  
N Rosenberg
Keyword(s):  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Hematological Diseases ◽  
Aggressive Disease ◽  
Disease Patterns ◽  
Cell Specificity ◽  
Different Types ◽  
Indolent Disease

Two forms of activated BCR/ABL proteins, P210 and P185, that differ in BCR-derived sequences, are associated with Philadelphia chromosome-positive leukemias. One of these diseases is chronic myelogenous leukemia, an indolent disease arising in hematopoietic stem cells that is almost always associated with the P210 form of BCR/ABL. Acute lymphocytic leukemia, a more aggressive malignancy, can be associated with both forms of BCR/ABL. While it is virtually certain that BCR/ABL plays a central role in both of these diseases, the features that determine the association of a particular form with a given disease have not been elucidated. We have used the bone marrow reconstitution leukemogenesis model to test the hypothesis that BCR sequences influence the ability of activated ABL to transform different types of hematopoietic cells. Our studies reveal that both P185 and P210 induce a similar spectrum of hematological diseases, including granulocytic, myelomonocytic, and lymphocytic leukemias. Despite the similarity of the disease patterns, animals given P185-infected marrow developed a more aggressive disease after a shorter latent period than those given P210-infected marrow. These data demonstrate that the structure of the BCR/ABL oncoprotein does not affect the type of disease induced by each form of the oncogene but does control the potency of the oncogenic signal.

scholarly journals Expression of leukocyte alkaline phosphatase gene in normal and leukemic cells: regulation of the transcript by granulocyte colony- stimulating factor

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2565-2571 ◽  
Author(s):  
A Rambaldi ◽  
M Terao ◽  
S Bettoni ◽  
ML Tini ◽  
R Bassan ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Polymorphonuclear Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Leukocyte Alkaline Phosphatase ◽  
Stimulating Factor

Abstract The levels of leukocyte alkaline phosphatase (LAP) messenger RNA (mRNA) are evaluated in B and T lymphocytes, monocytes, and polymorphonuclear cells (PMNs), and this transcript is found to be present only in PMNs. Precursors of the myelomonocytic pathway, represented by leukemic cells isolated from several cases of chronic myelogenous leukemia (CML) in its stable and blastic phase and acute myelogenous leukemia (AML), are devoid of LAP transcript. These data support the notion that LAP is a marker of the granulocyte terminal differentiation. Despite the absence of LAP mRNA in both the myeloid and the lymphoid precursors, nuclear run-on experiments show constitutive transcription of the LAP gene in leukemic cells obtained from AML, CML, as well as acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia (B-CLL). In CML and in chronic myelo-monocytic leukemia (CMML) PMNs, granulocyte colony- stimulating factor (G-CSF) specifically accumulates LAP mRNA without showing a substantial increase in the rate of transcription of the LAP gene. Once increased by G-CSF, LAP mRNA is very stable, showing a half- life of more than 4 hours in the presence of actinomycin-D. G-CSF is suggested to play a pivotal role in the modulation of LAP transcript in PMNs.

scholarly journals Deoxyribonucleoside triphosphate accumulation by leukemic cells

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 419-424 ◽  
Author(s):  
BS Mitchell ◽  
NL Edwards ◽  
CA Koller
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adenosine Deaminase ◽  
Lymphoblastic Leukemia ◽  
Chemotherapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Culture Cells ◽  
Acute Nonlymphoblastic Leukemia ◽  
Deoxyribonucleoside Triphosphate

Abstract The toxicity of the deoxyribonucleosides, 2′-deoxyadenosine, 2′- deoxyguanosine, and thymidine, for human T lymphoblasts is mediated by the accumulation of the corresponding deoxyribonucleoside triphosphate (dATP, dGTP, or dTTP, respectively). We have examined whether leukemic cells of non-T-cell origin are capable of accumulating deoxyribonucleotides in culture and whether this capability correlates with the activities of purine metabolizing enzymes in these cells. We have found that non-T, non-B acute lymphoblastic leukemia cells with low ecto-5′-nucleotidase and high adenosine deaminase activities increase their dATP pools by greater than tenfold when exposed to deoxyadenosine and an inhibitor of adenosine deaminase in culture. Cells from 2 of 9 patients with chronic lymphocytic leukemia and 4 of 11 patients with acute nonlymphoblastic leukemia achieved similar elevations in dATP, but there was no relationship between dATP accumulation and adenosine deaminase, purine nucleoside phosphorylase, or ecto-5′-nucleotidase activities. Treatment of four individuals with acute lymphoblastic leukemia with the adenosine deaminase inhibitor, 2′- deoxycoformycin, resulted in elevations in plasma deoxyadenosine concentrations and in increments in lymphoblast dATP levels that were similar to those measured in lymphoblasts cultured with deoxyadenosine and deoxycoformycin prior to treatment. In vitro incubations of leukemic cells with deoxyribonucleosides may provide a rational basis for the use of these compounds as chemotherapeutic agents.

Analysis of Four Types of Leukemia Using Gene Ontology Term and Kyoto Encyclopedia of Genes and Genomes Pathway Enrichment Scores

2020 ◽  
Vol 23 (4) ◽  
pp. 295-303
Author(s):  
Jing Lu ◽  
YuHang Zhang ◽  
ShaoPeng Wang ◽  
Yi Bi ◽  
Tao Huang ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Lymphoblastic Leukemia ◽  
Feature Selection Method ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Ontology Term ◽  
Kegg Pathways ◽  
Different Types ◽  
First Time ◽  
Go Terms

Aim and Objective: Leukemia is the second common blood cancer after lymphoma, and its incidence rate has an increasing trend in recent years. Leukemia can be classified into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myelogenous leukemia (CML). More than forty drugs are applicable to different types of leukemia based on the discrepant pathogenesis. Therefore, the identification of specific drug-targeted biological processes and pathways is helpful to determinate the underlying pathogenesis among such four types of leukemia. Methods: In this study, the gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were highly related to drugs for leukemia were investigated for the first time. The enrichment scores for associated GO terms and KEGG pathways were calculated to evaluate the drugs and leukemia. The feature selection method, minimum redundancy maximum relevance (mRMR), was used to analyze and identify important GO terms and KEGG pathways. Results: Twenty Go terms and two KEGG pathways with high scores have all been confirmed to effectively distinguish four types of leukemia. Conclusion: This analysis may provide a useful tool for the discrepant pathogenesis and drug design of different types of leukemia.

scholarly journals Plasma and urine cyclic nucleotide levels in patients with acute and chronic leukemia

Blood ◽  
1983 ◽  
Vol 61 (3) ◽  
pp. 429-434 ◽  
Author(s):  
M Peracchi ◽  
L Lombardi ◽  
AT Maiolo ◽  
F Bamonti-Catena ◽  
V Toschi ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Cyclic Nucleotide ◽  
Lymphoblastic Leukemia ◽  
Normal Subjects ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Response To Treatment ◽  
Deficiency Anemia ◽  
Additional Parameter ◽  
Acute Myelogenous

Abstract Plasma and urine levels of cyclic adenosine 3′,5′-monophosphate (cAMP) and of cyclic guanosine 3′,5′-monophosphate (cGMP) were measured in 35 normal subjects, in 24 patients with nonneoplastic diseases (iron deficiency anemia, peptic ulcer, and cholelithiasis), and in 50 leukemic patients. The leukemic group included patients with acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia. All patients were recently diagnosed and untreated, except for 5 patients with blastic transformation of chronic myelogenous leukemia who had been previously treated. There were no significant differences in plasma and urine cyclic nucleotide levels between normal subjects and patients with nonneoplastic diseases. In leukemic patients, plasma and urine cAMP levels were similar to those of normal subjects, whereas plasma and urine cGMP levels were markedly elevated. There were no significant differences in cGMP values between the various types of leukemia. After starting treatment, plasma cyclic nucleotide levels were periodically measured in 21 of the patients with acute leukemia; cGMP levels were normalized in all the 16 subjects who attained complete remission, whereas both cAMP and cGMP levels were apparently unaffected in the patients who did not respond to treatment. This suggests that plasma or urine cGMP could be used as an additional parameter to monitor the patient's response to treatment.

scholarly journals Changes of Dentition State in Leukemic Patients during Chemotherapy

2021 ◽  
Vol 18 (15) ◽  
pp. 8193
Author(s):  
Maja Ptasiewicz ◽  
Paweł Maksymiuk ◽  
Renata Chałas
Keyword(s):  
Dental Treatment ◽  
Case Reports ◽  
Lymphoblastic Leukemia ◽  
Hematological Parameters ◽  
Blood Parameters ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
University Hospital ◽  
Treatment Needs ◽  
Systemic Complications

A number of systemic diseases including hematological disorders have manifestations in the oral cavity region. These manifestations may often represent early signs of the underlying hematopoietic disease and occur frequently in leukemia. Despite the fact that leukemia has long been known to be associated with oral health deterioration, the available literature on this topic consists mostly of case reports, without data to conclude these. The aim of the study was to assess dentition state in leukemic patients during one cycle of chemotherapy and its correlation with blood parameters. The study included 102 adults treated because of leukemia at the Clinic of Haemato-Oncology and Bone Marrow Transplantation at the university hospital in Lublin, Poland. The sample group consisted of 51 women and 51 men aged 22 to 72 (54.07 ± 10.33) with following diagnoses: Acute myelogenous leukemia (AML)—55 patients (53.92%), Chronic lymphocytic leukemia (CLL)—17 patients (16.67%), Acute lymphoblastic leukemia (ALL)—16 patients (15.69%), Chronic myelogenous leukemia (CML)—10 patients (9.80%), Acute promyelocytic leukemia (APL) —3 patients (2.94%), Chronic hairy cell leukemia (HCL)—1 patient (0.98%). DMFT index was used to assess dentition state. After the cycle of chemotherapy, their dentition state changed in terms of decayed, missing and filled teeth and correlated with hematological parameters. Adult patients with leukemia have high dental treatment needs, and high number of missing teeth; thus, a comprehensive and fast dental treatment is necessary to avoid systemic complications and ensure better quality of life.

scholarly journals Expression of leukocyte alkaline phosphatase gene in normal and leukemic cells: regulation of the transcript by granulocyte colony- stimulating factor

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2565-2571 ◽  
Author(s):  
A Rambaldi ◽  
M Terao ◽  
S Bettoni ◽  
ML Tini ◽  
R Bassan ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Lymphoblastic Leukemia ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Polymorphonuclear Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Leukocyte Alkaline Phosphatase ◽  
Stimulating Factor

The levels of leukocyte alkaline phosphatase (LAP) messenger RNA (mRNA) are evaluated in B and T lymphocytes, monocytes, and polymorphonuclear cells (PMNs), and this transcript is found to be present only in PMNs. Precursors of the myelomonocytic pathway, represented by leukemic cells isolated from several cases of chronic myelogenous leukemia (CML) in its stable and blastic phase and acute myelogenous leukemia (AML), are devoid of LAP transcript. These data support the notion that LAP is a marker of the granulocyte terminal differentiation. Despite the absence of LAP mRNA in both the myeloid and the lymphoid precursors, nuclear run-on experiments show constitutive transcription of the LAP gene in leukemic cells obtained from AML, CML, as well as acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia (B-CLL). In CML and in chronic myelo-monocytic leukemia (CMML) PMNs, granulocyte colony- stimulating factor (G-CSF) specifically accumulates LAP mRNA without showing a substantial increase in the rate of transcription of the LAP gene. Once increased by G-CSF, LAP mRNA is very stable, showing a half- life of more than 4 hours in the presence of actinomycin-D. G-CSF is suggested to play a pivotal role in the modulation of LAP transcript in PMNs.

XmAb Fc engineered anti-CD19 monoclonal antibodies with enhanced in vitro efficacy against multiple lymphoma cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3021-3021
Author(s):  
E. Zhukovsky ◽  
S. Chu ◽  
M. Bernett ◽  
S. Karki ◽  
W. Dang ◽  
...  
Keyword(s):  
Cell Surface ◽  
B Cell ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Effector Function ◽  
Antibody Engineering ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Cell Surface Receptor

3021 Background: CD19 is a pan-B cell surface receptor that is expressed from early stages of pre-B cell development through terminal differentiation into plasma cells. It is an attractive immunotherapy target for cancers of lymphoid origin since it is also expressed on the vast majority of Non-Hodgkin Lymphoma (NHL) cells as well as some leukemias. Despite major improvements in response rates and progression free survival the majority of NHL patients will relapse under the current combination chemotherapy with anti-CD20. Thus salvage regimens with new non-cross resistant antibody therapies are warranted. Methods: We employ our XmAb antibody engineering technology to increase the affinity of IgG antibodies for Fc gamma receptors (FcγR), improve the effector function of antibodies, and significantly increases their antitumor potency; we also we humanize and affinity mature such antibodies. Results: The XmAb technology was applied to a humanized anti-CD19 antibody to engineer a variant with significantly enhanced (10- to 100-fold) antibody-dependent cell-mediated cytotoxicity (ADCC). The resulting XmAb CD19 variant was assayed for ADCC against multiple cell lines representative of follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), B-cell acute lymphoblastic leukemia (B-ALL), mantle cell lymphoma (MCL), hairy cell leukemia (HCL), chronic myelogenous leukemia (CML), and Burkitt’s lymphoma (BL). The ADCC activity of the XmAb CD19 was in striking contrast to a wild type IgG1 version of the antibody that mediates little ADCC. Moreover, ADCC potency and efficacy of the anti-CD19 Fc variant antibody were superior to that of rituximab: CLL - 10- and 1.5-fold higher, ALL - 10- and 100-fold higher, and HCL - 6- and 1.2-fold higher, respectively. Further, we observed no correlation between ADCC and antigen expression based on the measured cell surface density of CD19 for these cell lines. Conclusions: The increased affinity for FcγRs exhibited by the anti-CD19 Fc variant antibody overcomes much of the dependence of cytotoxicity on surface antigen density. Our data suggest that the anti-CD19 Fc variant antibody engineered for increased effector function could be a promising next-generation NHL immunotherapeutic. No significant financial relationships to disclose.

Compound GW506U78 in refractory hematologic malignancies: relationship between cellular pharmacokinetics and clinical response.

1998 ◽  
Vol 16 (11) ◽  
pp. 3607-3615 ◽  
Author(s):  
V Gandhi ◽  
W Plunkett ◽  
C O Rodriguez ◽  
B J Nowak ◽  
M Du ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Peak Plasma ◽  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Cancer Center ◽  
Pharmacokinetic Studies

PURPOSE In vitro investigations with arabinosylguanine (ara-G) demonstrated potent cytotoxicity to T-lymphoblastoid cell lines. The goals of the present study were to evaluate GW506U78, a prodrug of ara-G, against human hematologic malignancies and to determine its pharmacokinetics in plasma and cells. PATIENTS AND METHODS During a phase I multicenter trial of GW506U78, 26 patients were treated at M.D. Anderson Cancer Center (MDACC). Daily doses between 20 and 60 mg/kg were administered for 5 days. Parallel plasma and cellular pharmacokinetic studies were conducted. RESULTS Complete (n=5) or partial remission (n=5) was achieved in T-cell acute lymphoblastic leukemia (T-ALL), T-lymphoid blast crisis, T-lymphoma, and B-cell chronic lymphocytic leukemia (B-CLL) (n=13). In contrast, patients with B-ALL, B-lymphoma, acute myelogenous leukemia (AMI), or T-CLL did not respond. Peak plasma concentrations of GW506U78 and ara-G were dose-dependent. The elimination of GW506U78 (half-life [t1/2]=17 minutes) was faster than the elimination of ara-G (t1/2=3.7 hours). Median peak concentrations of ara-GTP were 23, 42, 85, and 93 micromol/L at 20, 30, 40, and 60 mg/kg, respectively. T-lymphoblasts accumulated significantly (P=.0008) higher peak arabinsylguanosine triphosphate (ara-GTP) (median, 140 micromol/L; n=7) compared with other diagnoses (median, 50 micromol/L; n=9) and normal mononuclear cells (n=3). The ara-GTP elimination was slow in all diagnoses (median, > 24 hours). Responders accumulated significantly (P=.0005) higher levels of ara-GTP (median, 157 micromol/L) compared with patients who failed to respond (median, 44 micromol/L). CONCLUSION GW506U78 is an effective prodrug and a potent agent for hematologic malignancies with major efficacy in T-cell diseases. The pharmacokinetics of ara-GTP in leukemia cells are strongly correlated with clinical responses to GW506U78.

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