Apoptotic effect of Bulbine Natalensis and Chlorophytum Comosum in myelogenous Leukemia K562 cell line

Bulbine natalensis and Chorophytum comosum are potential medicinal source for the treatment of cancers. Chronic myeloid leukaemia is a hematopoietic stem cells disorder treated by tyrosine kinase inhibitors but often cause recurrence of the leukaemia after cessation of therapy, hence require alternative treatment. This study determines the anti-cancer effect of leaf, root and bulb methanolic and aqueous extracts of B. natalensis and C. comosum in chronic human myelogenous leukaemia (K562) cell line by MTT, Hoechst bis-benzimide nuclear and annexin V stain assays. The root methanolic extract of B. natalensis and C. comosum showed a high cytotoxicity of 8.6% and 16.7% respectively on the K562 cell line at 1,000 μg/ml concentration. Morphological loss of cell membrane integrity causing degradation of the cell and fragmentation were observed in the root methanolic extract of both plants. A high apoptosis (p < 0.0001) was induced in the K562 cells by both leaf and root extracts of the C. comosum compared to the B. natalensis. This study shows both plants possess apoptotic effect against in vitro myelogenous leukaemia which contributes to the overall anti-cancer properties of B. natalensis and C. comosum to justify future therapeutic applications against chronic myelogenous leukaemia blood cancer.

Correlation of Bone Marrow Morphology and Immunophenotyping in Acute Leukaemia Patients

Background: Acute leukaemia (AL) is a malignant disorder of the blood that is characterized by blocked or impaired differentiation of haemopoietic stem cells, resulting in abnormal accumulation of immature precursors and suppression of growth and maturation of cells in vivo. Objective: To find out correlation between morphological and immunophenotypic study of bone marrow among acute leukaemia patient. Methods/Procedure: This is a comparative cross sectional study of diagnosis of leukaemia by bone marrow study and immunophenotyping from bone marrow sample with bone marrow alone of suspected cases of leukaemia treated in the department of haematology in Dhaka Medical College Hospital (DMCH)from March 2013 to August 2013 .Bone marrow examination and immunophenotyping was done simultaneously but having bone marrow morphology report we have compared with flow report. Results: Out of 50 patients according to Bone marrow study (BMS) 25(50.0%) of the patients had acute myelogenous leukaemia, 24(48.0%) had acute lymphoblastic leukaemia and 1(2.0%) had acute leukaemia. On the other hand, in immunophenotyping 28(56.0%) patients had acute lymphoblastic leukaemia, 20(40.0%) had acute myelogenous leukaemia and 2(4.0%) mixed cell immunophenotyping. Discordance of diagnosis was found in 3(6%) is diagnose as AML which was ALL on flow and one acute leukaemia and one AML was subsequently diagnose as mixed cellular leukaemia. Conclusion: Subjective variation in the accuracy of diagnosis of leukaemia on the basis of bone marrow study alone may occur. Inclusion of immunophenotyping with bone marrow study improves accuracy of leukaemia.

Coexistence of multiple myeloma and chronic myeloleukosis in one patient

Intoduction. Multiple myeloma (MM) and chronic myelogenous leukaemia (CML) are two haematological malignancies developing through tumour transformation of lymphoid and myeloid progenitor cells, respectively, not sharing a common ancestry. Coexistence of the two diseases is extremely rare.Aim. Clinical description of a patient diagnosed with CML in a few months after start of MM therapy.Main findings. We report a clinical case of MM and CML in a 62 years-old female patient. MM was diagnosed newly and followed by 5 VD chemotherapy cycles. Treatment discontinued due to severe polyneuropathy. The patient was transferred to thalidomide maintenance therapy. CML was diagnosed 12 months after initiation of thalidomide therapy: BCR-ABL (p190), BCR-ABL (p210). Since imatinib produced short-term effect, dasatinib therapy was started. Following 16 months after the onset of dasatinib therapy, MM relapse and CML progression were diagnosed.

The lysophospholipase D enzyme Gdpd3 is required to maintain chronic myelogenous leukaemia stem cells

Although advanced lipidomics technology facilitates quantitation of intracellular lipid components, little is known about the regulation of lipid metabolism in cancer cells. Here, we show that disruption of the Gdpd3 gene encoding a lysophospholipase D enzyme significantly decreased self-renewal capacity in murine chronic myelogenous leukaemia (CML) stem cells in vivo. Sophisticated lipidomics analyses revealed that Gdpd3 deficiency reduced levels of certain lysophosphatidic acids (LPAs) and lipid mediators in CML cells. Loss of Gdpd3 also activated AKT/mTORC1 signalling and cell cycle progression while suppressing Foxo3a/β-catenin interaction within CML stem cell nuclei. Strikingly, CML stem cells carrying a hypomorphic mutation of Lgr4/Gpr48, which encodes a leucine-rich repeat (LRR)-containing G-protein coupled receptor (GPCR) acting downstream of Gdpd3, displayed inadequate disease-initiating capacity in vivo. Our data showing that lysophospholipid metabolism is required for CML stem cell maintenance in vivo establish a new, biologically significant mechanism of cancer recurrence that is independent of oncogene addiction.

Pulmonary complications of Bcr-Abl tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKIs) targeting the Bcr-Abl oncoprotein revolutionised the treatment of chronic myelogenous leukaemia. Following the success of imatinib, second- and third-generation molecules were developed. Different profiles of kinase inhibition and off-target effects vary between TKIs, which leads to a broad spectrum of potential toxicities.Pulmonary complications are most frequently observed with dasatinib but all other Bcr-Abl TKIs have been implicated. Pleural effusions are the most frequent pulmonary complication of TKIs, usually associated with dasatinib and bosutinib. Pulmonary arterial hypertension is an uncommon but serious complication of dasatinib, which is often reversible upon discontinuation. Bosutinib and ponatinib have also been associated with pulmonary arterial hypertension, while imatinib has not. Rarely, interstitial lung disease has been associated with TKIs, predominantly with imatinib.Mechanistically, dasatinib affects maintenance of normal pulmonary endothelial integrity by generating mitochondrial oxidative stress, inducing endothelial apoptosis and impairing vascular permeability in a dose-dependent manner. The mechanisms underlying other TKI-related complications are largely unknown. Awareness and early diagnosis of the pulmonary complications of Bcr-Abl TKIs is essential given their seriousness, potential reversibility, and impact on future treatment options for the underlying chronic myelogenous leukaemia.