Impact of MLL::AF9 Gene Rearrangement on Survival of Acute Myeloid Leukaemia Patients: An Insight into Pakistani Population.

OBJECTIVE: To ascertain the frequency of the MLL::AF9 gene rearrangement and its association with survival in Pakistani patients suffering from acute myeloid leukaemia (AML). STUDY DESIGN: Analytical study. Place and Duration of the Study: Department of Haematology, National Institute of Blood Diseases and Bone Marrow Transplantation, Karachi, Pakistan, from 2015 to 2020. METHODOLOGY: Patients without a history of past AML chemotherapy, aged from 10 to 75 years, were included. Individuals with metastatic cancer, chronic myeloid leukaemia, or other haematological conditions were excluded. Identifying the MLL::AF9 gene involved RNA extraction, cDNA synthesis, and Real-time PCR amplification. The Chi-square test was used to examine the relationship between survival and the MLL::AF9 mutation. A Welch two-sample t-test was used to evaluate survival days depending on the MLL::AF9 gene rearrangement, while ANOVA was used to analyse survival days across various death statuses. RESULTS: The mean age of 130 patients was 36.65 ± 13.01 years, with 64.62% being males. The most common leukaemia type was AML-M2 (n = 32, 24.62%). During the study follow-up, 22.31% were still alive, 40.77% died, and the status of 36.92% were unknown. MLL::AF9 gene rearrangement was present in 11.54%. The group with MLL::AF9 gene rearrangement had significantly longer mean 'survival days' (1,542.33 ± 926.07) compared to the group without the gene rearrangement (206.42 ± 359.57, p <0.001). CONCLUSION: MLL-AF9 mutation was present in 11.54%. Age and MLL::AF9 gene rearrangement were significant predictors of survival in leukaemia patients. KEY WORDS: Acute myeloid leukaemia, MLL::AF9, Gene rearrangement, Survival.

P-Loop mutations-Negative prognosticators in tyrosine kinase inhibitors resistant chronic myeloid leukemia patients.

INTRODUCTION: P-Loop mutations in CML patients prevent the conformational change in BCR-ABL1 necessary for drug binding. The present study aimed to evaluate the impact of mutations in this domain on the prognosis of the disease and also to associate the baseline Sokal relative risk score with the overall survival in non-responding CML patients. METHODS: Blood samples were analyzed using ARMS-PCR and then an association was assessed between presence/absence of mutations, hematological and molecular response, disease progression, overall survival, and Sokal score. RESULTS: Of the total 250 CML patients, 102 were found to be treatment-resistant. Fifty-three patients harbored P-Loop mutations with G250E (12.7%) being most frequent. Complete hematological response and major molecular response were achieved by only 27.7% and 5.7 patients, respectively. Worst survival (57.1%) was observed in Y253H positive patients while according to Sokal score in high-risk patients harboring Y253F (50%) and E255V (50%). CONCLUSION: The presence of P-Loop domain mutations negatively impacted the prognosis of the disease in terms of disease advancement and overall survival. So, the timely performance of the BCR-ABL1 mutational analysis and the modifications in the treatment plan based on the mutation identified would help in a better outcome of the disease.

The relevance of economic freedom for energy, environment, and economic growth in Asia-Pacific region.

This paper investigates the relationship between energy intensity, economic freedom, and carbon emissions. The problem of environmental degradation, economic freedom, and energy use is mainly studied for developed economies; however, this study has selected forty-one Asia-Pacific economies representing all income groups of the World Bank's classification. In the presence of income, economic freedom plays a dual role for environment and energy: direct impact and as moderating factor impact. Here, we empirically test for a panel of 41 Asia-Pacific countries using the autoregressive distributed lag approach. Our findings suggest, although there is no bidirectional causality between all the variables, the long-run estimates of economic freedom for economy and environment are positive. The results imply for substantial structural reforms with a favorable economic and regulatory environment for Asia-Pacific countries. Our empirical analysis also implies that GDP growth levels for Asia-Pacific countries are becoming increasingly dependent on economic freedom and energy intensity. The results underline the critical role played directly and indirectly by economic freedom in creating an atmosphere that promotes research and development activities to help reduce energy intensity shortly to solve environmental problems.

Towards Achieving Sustainable Development: Role of Technology Innovation, Technology Adoption and CO2 Emission for BRICS.

In the digital era, technology innovation and adoption trigger economic growth and enhance CO2 emissions through productivity, which places it in the mainstream policy debate. For BRICS economies, this paper uses the first method proposed in the literature to quantify their information and communication technology (ICT) and innovatively links each country to their information technology adoption rate, as a surrogate indicator for measuring information and communication technology. Environmental Kuznets curve evidence is also examined, using technology innovation, technology adoption, and trade openness as the control variables for sustainable development. The results show that two out of three technology innovation instruments, fixed telephone, and broadband subscriptions increase CO2 emissions. Simultaneously, mobile cellular subscriptions have a lowering effect on CO2 emission in BRICS. The technology adoption indicators, high-technology exports, and electric power consumption also cause an upsurge in CO2 emission. Moreover, trade openness also enriches the level of CO2 emission in the BRICS regions. There is a need to devise technology innovation and adoption policies to better use technology and to ensure a green environment.

Energy capacity, industrial production, and the environment: an empirical analysis from Pakistan.

This paper aims to find out relationships among the energy, environment, and the industrial production for a developing country which is in earlier stages of development. It also tests a few contradicting hypotheses to find the possible shape of an environmental Kuznets curve. Using the time series data, the study finds robust long-run relationships between energy, environment, and industrial production for Pakistan. The scale economy is also assumed. It is also found that the capital and labor elasticities of income show increasing returns in the presence of energy and emission variables. It finds evidence of EKC in a quadratic restricted model but not in a cubic function. This analysis implies that the focus of policy authorities should be to persuade environment-friendly energy resources. After an initial stage of economic development, society has to take serious measure to tackle the issues of environmental degradation.

Outcome of Inversion 16 in TKD Positive and Negative Acute Myeloid Leukemia Patients.

abstract.

Chronic Myeloid Leukemia--Prognostic Value of Mutations.

Chronic myeloid leukemia (CML) is a stem cell disorder characterized by unrestricted proliferation of the myeloid series that occurs due to the BCR-ABL fusion oncogene as a result of reciprocal translocation t(9;22) (q34;q11). This discovery has made this particular domain a target for future efforts to cure CML. Imatinib revolutionized the treatment options for CML and gave encouraging results both in case of safety as well as tolerability profile as compared to agents such as hydroxyurea or busulfan given before Imatinib. However, about 2-4% of patients show resistance and mutations have been found to be one of the reasons for its development. European Leukemianet gives recommendations for BCR-ABL mutational analysis along with other tyrosine kinase inhibitors (TKIs) that should be administered according to the mutations harbored in a patient. The following overview gives recommendations for monitoring patients on the basis of their mutational status.

Prognostic involvement of nucleophosmin mutations in acute myeloid leaukemia.

Nucleophosmin (NPM1) is a protein of highly conserved nature which works as a molecular chaperone and is mostly found in nucleoli. NPM also involved in the maturation of preribosomes and duplication of centrosomes. Furthermore, it is also active in control and regulation of the ARF-p53 tumor suppressor pathway. A high rate of incidence and prognostic involvement is reported by various authors in AML patients. In AML it behaves as a favorable prognostic marker. NPM mutations are more frequently associated with normal-karyotype AML and are usually absent in patients having abnormal or poor cytogenetic. NPM mutations are not frequent in other hematopoietic tumors .Two main types of mutations have been described to date. Both of these cause abnormal cytoplasmic localization of NPM1. Their high incidence rate in normal karyoptype and their favorable nature make those mutations hot spot or front face mutations which should be checked before treatment starts.

Molecular involvement and prognostic importance of fms-like tyrosine kinase 3 in acute myeloid leukemia.

AML (Acute myeloid leukemia) is a form of blood cancer where growth of myeloid cells occurs in the bone marrow. The prognosis is poor in general for many reasons. One is the presence of leukaemia-specific recognition markers such as FLT3 (fms-like tyrosine kinase 3). Another name of FLT3 is stem cell tyrosine kinase-1 (STK1), which is known to take part in proliferation, differentiation and apoptosis of hematopoietic cells, usually being present on haemopoietic progenitor cells in the bone marrow. FLT3 act as an independent prognostic factor for AML. Although a vast literature is available about the association of FLT3 with AML there still is a need of a brief up to date overview which draw a clear picture about this association and their effect on overall survival.