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  1. Article ; Online: Influence of cytochrome P450 and glutathione S transferase polymorphisms on response to nilotinib therapy among chronic myeloidleukemia patients from Pakistan.

    Mukry, Samina Naz / Shahni, Aneeta / Zaidi, Uzma / Sultan Shamsi, Tahir

    BMC cancer

    2022  Volume 22, Issue 1, Page(s) 519

    Abstract: Background: Cytochrome P450 (CYP) and glutathione S transferases (GSTs) are important biotransforming enzymes responsible for detoxification of anticancer drugs and carcinogens. Polymorphisms in these enzymes may greatly influence the susceptibility to ... ...

    Abstract Background: Cytochrome P450 (CYP) and glutathione S transferases (GSTs) are important biotransforming enzymes responsible for detoxification of anticancer drugs and carcinogens. Polymorphisms in these enzymes may greatly influence the susceptibility to CML and overall efficacy of tyrosine kinase inhibitors. This study was aimed to estimate the possible influence of the polymorphisms of GSTs and CYP in the occurrence of CML as well as in predicting therapeutic outcome of nilotinib therapy in Pakistani CML patients.
    Methods: The polymorphic variability in CYP 1A1*2C, GSTP1 (A3131G), GSTT1 and GSTM1 was assessed either by RFLP or multiplex PCR. The BCR ABL1 transcripts were quantified by qPCR to monitor response to nilotinib.
    Results: The CYP1A1*2C heterozygous and GSTP1 homozygous polymorphisms seemed to be a contributing factor in developing CML. Altogether, there were 12 non-responders, 66 responders and 21 partial responders. The most frequent genotype was null GSTM1 in responders followed by CYP 1A1 and GSTP1 -wild type (p =  < 0.05). Whereas, homozygous GSTP1 and GSTT1 null genotype is significantly higher only among nilotinib non-responders.
    Conclusion: Hence, it can be concluded that wild type CYP1A1, GSTP1 and null GSTM1 may be frequently linked to favorable outcome in patients treated with nilotinib as depicted by sustained deep molecular response in most CML patients.
    MeSH term(s) Case-Control Studies ; Cytochrome P-450 CYP1A1/genetics ; Genetic Predisposition to Disease ; Genotype ; Glutathione S-Transferase pi/genetics ; Glutathione Transferase/genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Pakistan ; Polymorphism, Genetic ; Pyrimidines/therapeutic use ; Risk Factors
    Chemical Substances Pyrimidines ; Cytochrome P-450 CYP1A1 (EC 1.14.14.1) ; glutathione S-transferase T1 (EC 2.5.1.-) ; GSTP1 protein, human (EC 2.5.1.18) ; Glutathione S-Transferase pi (EC 2.5.1.18) ; Glutathione Transferase (EC 2.5.1.18) ; glutathione S-transferase M1 (EC 2.5.1.18) ; nilotinib (F41401512X)
    Language English
    Publishing date 2022-05-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041352-X
    ISSN 1471-2407 ; 1471-2407
    ISSN (online) 1471-2407
    ISSN 1471-2407
    DOI 10.1186/s12885-022-09605-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Expression of aberrant antigens in hematological malignancies: A single center experience.

    Shahni, Aneeta / Saud, Madiha / Siddiqui, Saima / Mukry, Samina Naz

    Pakistan journal of medical sciences

    2018  Volume 34, Issue 2, Page(s) 457–462

    Abstract: Background and objective: Aberrant phenotype is a phenomenon of abnormal expression or loss of expression of cell specific lineage marker not associated with specific cell type. Aberrant phenotype expression due to genetic defects may be associated with ...

    Abstract Background and objective: Aberrant phenotype is a phenomenon of abnormal expression or loss of expression of cell specific lineage marker not associated with specific cell type. Aberrant phenotype expression due to genetic defects may be associated with unfavorable outcome. It can be used to determine minimal residual disease status. The purpose of the study was to find out the occurrence of aberrant phenotypes in leukemia/lymphoma patients.
    Methods: One milliliter peripheral blood or bone marrow samples were analyzed on FACS Calibur flowcytometer. The cells were lysed and stained following standard protocol. Data was acquired and analyzed by CellQuest-Pro software. The Antigenic expression was rated as positive when the percentage of positive blast cells was ≥ 20%. In that manner, aberrant phenotype was considered positive when 20% of blast cells show expression of markers.
    Results: Of a total 145 cases analyzed, 26 were acute myeloid leukemia, 71 of acute lymphoblastic leukaemia, 48 were of Chronic Lymphoid leukemia on the basis of morphological features and confirmed by flow cytometry. Overall, 19% (28) cases showed aberrant expression of antigens. In 32% (9/28) AML patients, CD5, CD7, CD64dim, CD10, CD117, CD25 and TdT were expressed while in 25% (7/28) ALL patients CD33, CD13, HLA-DR and CD3 were detected. Among chronic leukemia, all aberrant expressions were seen in cases of B-CLL (10/28) only; with CD11c, CD3 and CD10 as the aberrantly expressed markers.
    Conclusion: Variability in aberrant phenotype expression was observed in different types of acute and chronic leukemia patients with no prognostic implications on treatment response.
    Language English
    Publishing date 2018-04-26
    Publishing country Pakistan
    Document type Journal Article
    ZDB-ID 2032827-8
    ISSN 1681-715X ; 1682-024X ; 1017-4699
    ISSN (online) 1681-715X
    ISSN 1682-024X ; 1017-4699
    DOI 10.12669/pjms.342.13996
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Jg. 1995 - 2021: Lesesall (2.OG)
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  3. Article ; Online: Sequencing of SARS-CoV-2 in local transmission cases through Oxford Nanopore MinION platform from Karachi Pakistan.

    Mukry, Samina Naz / Ahmed, Shariq / Raza Bukhari, Ali / Shahni, Aneeta / Sufaida, Gul / Naz, Arshi / Shamsi, Tahir Sultan

    Journal of infection in developing countries

    2021  Volume 15, Issue 10, Page(s) 1376–1383

    Abstract: Introduction: The first case of severe acute respiratory syndrome 2 (SARS-CoV-2) was imported to Pakistan in February 2020, since then 8,260 deaths have been witnessed. The virus has been constantly mutating and local transmission cases from different ... ...

    Abstract Introduction: The first case of severe acute respiratory syndrome 2 (SARS-CoV-2) was imported to Pakistan in February 2020, since then 8,260 deaths have been witnessed. The virus has been constantly mutating and local transmission cases from different countries vary due to host dependent viral adaptation. Many distinct clusters of variant SARS-CoV-2 have been defined globally. In this study, the epidemiology of SARS-CoV-2 was studied and locally transmitted SARS-CoV-2 isolates from Karachi were sequenced to compared and identify any possible variants.
    Methodology: The real time PCR was performed on nasopharyngeal specimen to confirm SARS-CoV-2 with Orf 1ab and E gene as targets. The virus isolates were sequenced through oxford nanopore technology MinION platform. Isolates from the first and second wave of COVID-19 outbreak in Karachi were compared.
    Results: The overall positivity rate for PCR was 26.24% with the highest number of positive cases in June. Approximately, 37.45% PCR positive subjects aged between 19-40 years. All the isolates belonged to GH clade and shared missense mutation D614G in spike protein linked to increased transmission rate worldwide. Another spike protein mutation A222V coexisted with D614G in the virus from the second wave of COVID-19.
    Conclusions: Based on the present findings it is suggested that the locally transmitted virus from Karachi varies from those reported from other parts of Pakistan. Slight variability was also observed between viruses from the first and second wave. Variability in any potential vaccine target may result in failed trials, therefore information on any local viral variants is always useful for effective vaccine design and/or selection.
    MeSH term(s) Adult ; COVID-19/epidemiology ; COVID-19/transmission ; COVID-19/virology ; Female ; Genome, Viral ; Humans ; Male ; Middle Aged ; Mutation ; Nanopores ; Nasopharynx/virology ; Pakistan ; Phylogeny ; Polymerase Chain Reaction ; SARS-CoV-2/genetics ; Whole Genome Sequencing/instrumentation ; Whole Genome Sequencing/methods ; Young Adult
    Language English
    Publishing date 2021-10-31
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2394024-4
    ISSN 1972-2680 ; 2036-6590
    ISSN (online) 1972-2680
    ISSN 2036-6590
    DOI 10.3855/jidc.14900
    Database MEDical Literature Analysis and Retrieval System OnLINE

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