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Mar 2023 DOI 10.14302/issn.2641-5518.jcci-23-4506
Partanen AnuCorresponding author
Limited data exist on the mechanisms promoting clonal expression of BCR-ABL1 cells in various myeloproliferative disorders. We present a patient whose Janus Kinase (JAK) 2 V617F-negative idiopathic myelofibrosis (IMF) transformed to Philadelphia-positive chronic myeloid leukemia (CML). A 55-year-old man had anemia and splenomegaly. Trephine biopsy showed excess fibrosis without a JAK2 V617F mutation. Diagnosis of high-risk IMF with t(3;12) and del(16q) was made. Five years later a repeated trephine biopsy showed extensive fibrosis and t(9;22) with der(22)t(9;22). BCR-ABL1 fusion gene with typical p210 fusion transcript was found resulting in the diagnosis of CML. A modest treatment response was achieved with tyrosine kinase inhibitor (TKI) therapies, but the disease eventually progressed to a myeloid blast phase. With AML-based chemotherapy plus azacytidine and a second generation TKI the patient survived for years but succumbed 11 years after the initial diagnosis. Clonal evolution may cause atypical disease characteristics or a poor response to targeted therapy in myeloproliferative disorders.
May 2015 DOI 10.14302/issn.2471-2175.jdrt-14-618
Y Chon SusanCorresponding author
Department of Dermatology, University of Texas MD Anderson Cancer Center
A case of a solitary necrotic cutaneous lesion in a neutropenic patient with acute myeloid leukemia is described. The report discusses infectious and non‑infectious differentials, work‑up under immunosuppression, and targeted management.
Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-358
Mandava SwarnaCorresponding author
Cytogenetic division, SRL Ltd., Mumbai, India.
Acute lymphoblastic leukemia (ALL) is a rapid form of leukemia characterized by clonal proliferation and accumulation of immature hematopoietic stem cells of the lymphoid lineage in the bone marrow as well as peripheral blood. Chromosomal aberrations identified in childhood ALL have an important role in disease diagnosis, prognosis and management. We present the results of hematologic, immunophenotypic, cytogenetic, FISH and Multiplex RT-PCR analysis of a 6-year-old boy diagnosed with B-cell precursor Acute Lymphoblastic Leukemia (BCP- ALL). In this study, we identified a novel chromosomal translocation t(10;15)(q22;q22) by cytogenetic and FISH analysis. To the best of our knowledge, this is the first report of this novel chromosomal translocation in this subset of ALL and has not yet been reported elsewhere. This rearrangement may include certain cancer associated tumor suppressor gene(s) or genes involved in apoptosis and transcription regulation, which on loss of normal function may lead to leukaemogenesis.
Apr 2022 DOI 10.14302/issn.2372-6601.jhor-22-4133
Qing XinCorresponding author
Department of Pathology, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA.
Background Monoclonal gammopathy of undetermined significance (MGUS) and chronic myeloid leukemia (CML) are diseases of different lineages. The diagnosis of both MGUS and CML in the same patient is a rare occurrence and has not been reported in much literature. Case Presentation We describe a 56-year-old man with a history of rheumatoid arthritis incidentally found to have an increase in IgA paraprotein. With less than 10% monoclonal plasma cells on the bone marrow biopsy and absence of hypercalcemia, renal failure, anemia and bone lesions, MGUS was diagnosed. The conventional cytogenetics at the time showed the presence of the Philadelphia chromosome in 30% of metaphases. However, there was no morphologic evidence of CML in the peripheral blood or bone marrow. Patient received no treatment and lost follow-up until 3 years later when a routine CBC showed leukocytosis and thrombocytosis. CML, chronic phase was diagnosed following a bone marrow aspiration and biopsy with Philadelphia chromosome observed in 100% of metaphases. Patient was treated with imatinib and later switched to dasatinib and complete molecular remission was continued to be achieved. Discussion and Conclusion Here we report a case of pre-leukemic CML as an incidental finding during the diagnosis of MGUS. The possible underlying mechanisms of the association are discussed although the exact cause of the coexistence is unclear.
Dec 2018 DOI 10.14302/issn.2381-862X.jwrh-18-2459
Jana SnehasisCorresponding author
Trivedi Science Research Laboratory Pvt. Ltd.,Bhopal, India
The objective of the study was to investigate the effect of Consciousness Energy Healing based DMEM medium on the level of alkaline phosphatase enzyme (ALP) activity in Ishikawa cells. The test item, DMEM medium was divided into two parts. One part of the test item received Consciousness Energy Healing Treatment by a renowned Biofield Energy Healer, Mahendra Kumar Trivedi and was labeled as the Biofield Energy Treated DMEM, while the other part did not receive any treatment, and defined as the untreated DMEM group. The cell viability using MTT assay of the Biofield Energy Treated DMEM group was observed as 108%, which indicated that the test item was safe and non-toxic. The estrogenic potential using ALP level showed a significantly increase by 73.21% in the Biofield Energy Treated DMEM group as compared to the untreated DMEM group. Overall, the experimental data suggested that the Biofield Energy Treated DMEM has significantly improved ALP level, which play a vital role for the promotion and maintenance of estrogen level. Based on the study outcomes, it is concluded that Biofield Energy Healing Treatment showed a significant improved ALP level, which can be used in various estrogenic disorders such as hypophosphatasia, osteoporosis, severe anemia, malnutrition, hypothyroidism, magnesium deficiency, heart surgery, aplastic anemia, chronic myelogenous leukemia, enteritis in children, Wilson’s disease, pernicious anemia, bacterial infection and intrauterine infection is a leading cause of pelvic inflammatory disease, subfertility, infertility, endometritis, early pregnancy loss, fetal defects, and preterm birth.
Feb 2018 DOI 10.14302/issn.2372-6601.jhor-18-1938
Mostafa Ali ElsayedCorresponding author
Clinical Oncology Department, Faculty of Medicine, Sohag University
Neuropilins are transmembrane glycoproteins that act as receptors for vascular endothelial growth factors (VEGF) and are involved in the process of tumor angiogenesis. Its importance in hematological malignancies such as acute leukemia (AL) remains to be elucidated. The aim of this study was to evaluate the significance of neuropilin-1 expression in acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients by flowcytometry and the difference between both groups of acute leukemia. Bone marrow aspirates of 52 patients with acute leukemia, 29 patients with de novo AML and 23 ALL patients were examined in this study. 15 subjects with non-hematological malignancy serving as the control group were also included. Neuropilin-1 expression by flow cytometry showed a highly significant increase in de novo AML and ALL patients with a mean of 37.9 ± 20.92% and 32.33±19.8%, respectively, compared to control group’s mean of 11.51 ± 3.04% (p= 0.001, 0.006). There were no statistically significanct difference between ALL and AML patients (p= 0.76). Neuropilin-1 surface expression by flowcytometry showed a significant positive correlation with total leukocyte count, bone marrow blast percentage, CD45 and CD14 and negative correlation with hemoglobin level, RBCs count in AML patients. In ALL patients, positive significant correlations were found with bone marrow blast percentage and negative correlation with hemoglobin level, RBCs count. Neuropilin-1expression was detected significantly in acute leukemias and it is related to the disease severity.
Nov 2017 DOI 10.14302/issn.2372-6601.jhor-17-1761
Lee Mortensen GitteCorresponding author
AnthroConsult, Fynsgade 24, 8000 Aarhus C, Denmark
With the introduction of tyrosine kinase inhibitors (TKI), patients with chronic myeloid leukemia (CML) have obtained survival rates close to normal. It may appear paradoxical, then, that medication adherence is suboptimal in some health care settings. As the first of its kind, this study aimed to explore drivers and barriers to TKI treatment adherence in Danish CML patients. A literature study informed the design of qualitative interviews with 20 patients, individually and in focus groups, focusing on their disease perceptions of CML, their health-related quality of life (QoL) and medication adherence. The study showed that many participants had previously switched treatment due to lacking efficacy or intolerance but most felt their current disease burden was tolerable. Anxiety might, however, resurface if treatment stopped working or with the occurrence of infections or side effects, creating a state of ‘fragile peace’. To these patients, their role functioning – as professionals, spouses, parents and grandparents – was crucial to uphold a positive self-image and meaningful life. Whether treatment enabled or hindered this was thus decisive to their QoL and medication adherence. Our participants expressed high adherence rates with only one having intentionally non-adhered due to side effects and poor QoL. Most participants felt well-informed about CML and treatment and privileged to receive specialised personal care from the public health care system acting to motivate their medication adherence. As a novel finding, this study indicates that the prospect of treatment-free remission may positively affect ‘adherence’ suggest this should be explored in future studies.
Dec 2016 DOI 10.14302/issn.2372-6601.jhor-16-1330
Ferrarini IsaccoCorresponding author
Section of Hematology, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
Immune thrombocytopenia (ITP) is a rare but well-recognized post-allogeneic hematopoietic stem cell transplant (HSCT) autoimmune complication for which a standard treatment approach is lacking. Herein we report on an adult patient affected by high-risk acute myeloid leukemia (AML) who developed a post-HSCT ITP. Due to the refractoriness to first-line therapies the patient underwent the thrombopoietin (TPO) mimetic Eltrombopag obtaining the ITP resolution. We also discuss the clinical course of ITP in post-HSCT setting and pros and cons of different therapeutic strategies, focusing on the emerging role of TPO mimetics.
Feb 2016 DOI 10.14302/issn.2372-6601.jhor-15-822
I.V. ChernikovCorresponding author
Institute of Chemical Biology and Fundamental Medicine SB RAS.
Small interfering RNA (siRNA) based drugs for overcoming multiple drug resistance of hematological malignancies could solve the problem of poor response to the chemotherapy and hight relapse rate. The main factor that significantly limits biomedical application of siRNA is inefficient delivery to target cells and tissues. The attachment of siRNA to molecules, which enter into the cell by natural transport mechanisms, can improve cellular uptake of siRNA. In current study the carrier-free cellular uptake of siRNA containig cholesterol residues conjugated to the 5’-end of the sense strand via oligomethylene linker of various length (here and after Ch-siRNA) was explored. The data demonstrate that cholesterol residue increase the accumulation of siRNA in all tested cell lines and the primary cells. The efficiency of Ch-siRNA accumulation in K562 cells depends greatly on the leangth of the linker connecting cholesterol and siRNA: Ch-siRNAs with linker of 10 - 12 methylene units accumulate the most efficiently in this cells. It was found that Ch-siRNA effectively accumulates in MOLT-3 (acute lymphoblastic leukemia, ALL), HL-60 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia CML) and primary peripheral blood mononuclear cells (PBMC) from patient with non-Hodgkin lymphoma (NHL) or healthy donor resulting in near 100% of transfected cell when used at 1 mM concentration.