bims-almceb Biomed News
on Acute Leukemia Metabolism and Cell Biology
Issue of 2023–04–02
fiveteen papers selected by
Camila Kehl Dias, Federal University of Rio Grande do Sul
  1. Editorial: Understanding mitochondrial dynamics and metabolic plasticity in cancer stem cells: Recent advances in cancer treatment and potential therapeutic approaches.
  2. Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation.
  3. FASN-deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress.
  4. Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients.
  5. Repurposing Verapamil to Enhance Killing of T-ALL Cells by the mTOR Inhibitor Everolimus.
  6. Metabolic reprogramming in cancer: Mechanisms and therapeutics.
  7. Amino acid metabolic reprogramming in tumor metastatic colonization.
  8. Simultaneous Inhibition of Ceramide Hydrolysis and Glycosylation Synergizes to Corrupt Mitochondrial Respiration and Signal Caspase Driven Cell Death in Drug-Resistant Acute Myeloid Leukemia.
  9. Ex vivo reprogramming of human hematopoietic stem cells is accompanied by increased transcripts of genes regulating metabolic integrity.
  10. The Role of Reprogrammed Glucose Metabolism in Cancer.
  11. Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.
  12. Editorial: Hallmark of cancer: Evasion of growth suppressors.
  13. Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade.
  14. Epigenetically programmed resistance to chemo- and immuno-therapies.
  15. Utility of Flow Cytometry in Diagnosis of Acute Leukemias: A Study at RIMS, Ranchi, India.
  1. Front Oncol. 2023 ;13 1155774
    Editorial: Understanding mitochondrial dynamics and metabolic plasticity in cancer stem cells: Recent advances in cancer treatment and potential therapeutic approaches.
    Pramod Darvin, Varun Sasidharan Nair.
      
    Keywords:  cancer stem cell (CSC); hypoxic microenvironment; mitochondrial dynamics; mitochondrial immune evasion; mitophagy
    DOI:  https://doi.org/10.3389/fonc.2023.1155774
  2. Leukemia. 2023 Mar 30.
    Tespa1 facilitates hematopoietic and leukemic stem cell maintenance by restricting c-Myc degradation.
    Yukai Lu, Lijing Yang, Mingqiang Shen, Zihao Zhang, Song Wang, Fang Chen, Naicheng Chen, Yang Xu, Hao Zeng, Mo Chen, Shilei Chen, Fengchao Wang, Mengjia Hu, Junping Wang.
      Hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have robust self-renewal potential, which is responsible for sustaining normal and malignant hematopoiesis, respectively. Although considerable efforts have been made to explore the regulation of HSC and LSC maintenance, the underlying molecular mechanism remains obscure. Here, we observe that the expression of thymocyte-expressed, positive selection-associated 1 (Tespa1) is markedly increased in HSCs after stresses exposure. Of note, deletion of Tespa1 results in short-term expansion but long-term exhaustion of HSCs in mice under stress conditions due to impaired quiescence. Mechanistically, Tespa1 can interact with CSN subunit 6 (CSN6), a subunit of COP9 signalosome, to prevent ubiquitination-mediated degradation of c-Myc protein in HSCs. As a consequence, forcing c-Myc expression improves the functional defect of Tespa1-null HSCs. On the other hand, Tespa1 is identified to be highly enriched in human acute myeloid leukemia (AML) cells and is essential for AML cell growth. Furthermore, using MLL-AF9-induced AML model, we find that Tespa1 deficiency suppresses leukemogenesis and LSC maintenance. In summary, our findings reveal the important role of Tespa1 in promoting HSC and LSC maintenance and therefore provide new insights on the feasibility of hematopoietic regeneration and AML treatment.
    DOI:  https://doi.org/10.1038/s41375-023-01880-6
  3. bioRxiv. 2023 Mar 15. pii: 2023.03.14.532533. [Epub ahead of print]
    FASN-deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress.
    Wenting Dai, Zhichao Wang, Guan Wang, Qiong A Wang, Ralph DeBerardinis, Lei Jiang.
      Fatty acid synthase (FASN) maintains de novo lipogenesis (DNL) to support rapid growth in most proliferating cancer cells. Lipogenic acetyl-CoA is primarily produced from carbohydrates but can arise from glutamine-dependent reductive carboxylation under hypoxia. Here we show that reductive carboxylation also occurs in the absence of DNL in cells with defective FASN. In this state, reductive carboxylation was mainly catalyzed by isocitrate dehydrogenase-1 (IDH1) in the cytosol, but IDH1-generated citrate was not used for DNL. Metabolic flux analysis (MFA) revealed that FASN-deficiency induced a net cytosol-to-mitochondria citrate flux through citrate transport protein (CTP). A similar pathway was previously shown to mitigate detachment-induced mitochondrial reactive oxygen species (mtROS) in anchorage-independent tumor spheroids. We further demonstrate that FASN-deficient cells acquire resistance to oxidative stress in a CTP- and IDH1-dependent manner. Together with the reduced FASN activity in tumor spheroids, these data indicate that anchorage-independent malignant cells trade FASN-supported rapid growth for a cytosol-to-mitochondria citrate flux to gain redox capacity against detachment-induced oxidative stress.
    DOI:  https://doi.org/10.1101/2023.03.14.532533
  4. Int J Mol Sci. 2023 Mar 22. pii: 5988. [Epub ahead of print]24(6):
    Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients.
    Caroline Lo Presti, Yoshiki Yamaryo-Botté, Julie Mondet, Sylvie Berthier, Denisa Nutiu, Cyrille Botté, Pascal Mossuz.
      Several studies have linked bad prognoses of acute myeloid leukemia (AML) to the ability of leukemic cells to reprogram their metabolism and, in particular, their lipid metabolism. In this context, we performed "in-depth" characterization of fatty acids (FAs) and lipid species in leukemic cell lines and in plasma from AML patients. We firstly showed that leukemic cell lines harbored significant differences in their lipid profiles at steady state, and that under nutrient stress, they developed common mechanisms of protection that led to variation in the same lipid species; this highlights that the remodeling of lipid species is a major and shared mechanism of adaptation to stress in leukemic cells. We also showed that sensitivity to etomoxir, which blocks fatty acid oxidation (FAO), was dependent on the initial lipid profile of cell lines, suggesting that only a particular "lipidic phenotype" is sensitive to the drug targeting of FAO. We then showed that the lipid profiles of plasma samples from AML patients were significantly correlated with the prognosis of patients. In particular, we highlighted the impact of phosphocholine and phosphatidyl-choline metabolism on patients' survival. In conclusion, our data show that balance between lipid species is a phenotypic marker of the diversity of leukemic cells that significantly influences their proliferation and resistance to stress, and thereby, the prognosis of AML patients.
    Keywords:  acute myeloid leukemia; inhibition of FAO; lipid species; metabolism
    DOI:  https://doi.org/10.3390/ijms24065988
  5. Antioxidants (Basel). 2023 Mar 03. pii: 625. [Epub ahead of print]12(3):
    Repurposing Verapamil to Enhance Killing of T-ALL Cells by the mTOR Inhibitor Everolimus.
    Micol Silic-Benussi, Evgeniya Sharova, Alberto Corradin, Loredana Urso, Vittoria Raimondi, Ilaria Cavallari, Barbara Buldini, Samuela Francescato, Sonia A Minuzzo, Donna M D'Agostino, Vincenzo Ciminale.
      New therapies are needed for patients with T-cell lymphoblastic leukemia (T-ALL) who do not respond to standard chemotherapy. Our previous studies showed that the mTORC1 inhibitor everolimus increases reactive oxygen species (ROS) levels, decreases the levels of NADPH and glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP), and induces apoptosis in T-ALL cells. Studies in T-ALL-xenografted NOD/SCID mice demonstrated that everolimus improved their response to the glucocorticoid (GC) dexamethasone. Here we show that verapamil, a calcium antagonist used in the treatment of supraventricular tachyarrhythmias, enhanced the effects of everolimus on ROS and cell death in T-ALL cell lines. The death-enhancing effect was synergistic and was confirmed in assays on a panel of therapy-resistant patient-derived xenografts (PDX) and primary samples from T-ALL patients. The verapamil-everolimus combination produced a dramatic reduction in the levels of G6PD and induction of p38 MAPK phosphorylation. Studies of NOD/SCID mice inoculated with refractory T-ALL PDX cells demonstrated that the addition of verapamil to everolimus plus dexamethasone significantly reduced tumor growth in vivo. Taken together, our results provide a rationale for repurposing verapamil in association with mTORC inhibitors and GC to treat refractory T-ALL.
    Keywords:  ROS; cell death; leukemia; pentose phosphate pathway
    DOI:  https://doi.org/10.3390/antiox12030625
  6. MedComm (2020). 2023 Apr;4(2): e218
    Metabolic reprogramming in cancer: Mechanisms and therapeutics.
    Shiqi Nong, Xiaoyue Han, Yu Xiang, Yuran Qian, Yuhao Wei, Tingyue Zhang, Keyue Tian, Kai Shen, Jing Yang, Xuelei Ma.
      Cancer cells characterized by uncontrolled growth and proliferation require altered metabolic processes to maintain this characteristic. Metabolic reprogramming is a process mediated by various factors, including oncogenes, tumor suppressor genes, changes in growth factors, and tumor-host cell interactions, which help to meet the needs of cancer cell anabolism and promote tumor development. Metabolic reprogramming in tumor cells is dynamically variable, depending on the tumor type and microenvironment, and reprogramming involves multiple metabolic pathways. These metabolic pathways have complex mechanisms and involve the coordination of various signaling molecules, proteins, and enzymes, which increases the resistance of tumor cells to traditional antitumor therapies. With the development of cancer therapies, metabolic reprogramming has been recognized as a new therapeutic target for metabolic changes in tumor cells. Therefore, understanding how multiple metabolic pathways in cancer cells change can provide a reference for the development of new therapies for tumor treatment. Here, we systemically reviewed the metabolic changes and their alteration factors, together with the current tumor regulation treatments and other possible treatments that are still under investigation. Continuous efforts are needed to further explore the mechanism of cancer metabolism reprogramming and corresponding metabolic treatments.
    Keywords:  cancer metabolism; cancer therapy; glycolysis; metabolic reprogramming
    DOI:  https://doi.org/10.1002/mco2.218
  7. Front Oncol. 2023 ;13 1123192
    Amino acid metabolic reprogramming in tumor metastatic colonization.
    Zihao Wang, Xingyun Wu, Hai-Ning Chen, Kui Wang.
      Metastasis is considered as the major cause of cancer death. Cancer cells can be released from primary tumors into the circulation and then colonize in distant organs. How cancer cells acquire the ability to colonize in distant organs has always been the focus of tumor biology. To enable survival and growth in the new environment, metastases commonly reprogram their metabolic states and therefore display different metabolic properties and preferences compared with the primary lesions. For different microenvironments in various colonization sites, cancer cells must transfer to specific metabolic states to colonize in different distant organs, which provides the possibility of evaluating metastasis tendency by tumor metabolic states. Amino acids provide crucial precursors for many biosynthesis and play an essential role in cancer metastasis. Evidence has proved the hyperactivation of several amino acid biosynthetic pathways in metastatic cancer cells, including glutamine, serine, glycine, branched chain amino acids (BCAAs), proline, and asparagine metabolism. The reprogramming of amino acid metabolism can orchestrate energy supply, redox homeostasis, and other metabolism-associated pathways during cancer metastasis. Here, we review the role and function of amino acid metabolic reprogramming in cancer cells colonizing in common metastatic organs, including lung, liver, brain, peritoneum, and bone. In addition, we summarize the current biomarker identification and drug development of cancer metastasis under the amino acid metabolism reprogramming, and discuss the possibility and prospect of targeting organ-specific metastasis for cancer treatment.
    Keywords:  amino acid metabolism; cancer metastasis; distant organ colonization; metabolic reprogramming; metabolic targeting
    DOI:  https://doi.org/10.3389/fonc.2023.1123192
  8. Cancers (Basel). 2023 Mar 21. pii: 1883. [Epub ahead of print]15(6):
    Simultaneous Inhibition of Ceramide Hydrolysis and Glycosylation Synergizes to Corrupt Mitochondrial Respiration and Signal Caspase Driven Cell Death in Drug-Resistant Acute Myeloid Leukemia.
    Kelsey H Fisher-Wellman, Miki Kassai, James T Hagen, P Darrell Neufer, Mark Kester, Thomas P Loughran, Charles E Chalfant, David J Feith, Su-Fern Tan, Todd E Fox, Johnson Ung, Gemma Fabrias, Jose' Luis Abad, Arati Sharma, Upendarrao Golla, David F Claxton, Jeremy J P Shaw, Debajit Bhowmick, Myles C Cabot.
      Acute myelogenous leukemia (AML), the most prevalent acute and aggressive leukemia diagnosed in adults, often recurs as a difficult-to-treat, chemotherapy-resistant disease. Because chemotherapy resistance is a major obstacle to successful treatment, novel therapeutic intervention is needed. Upregulated ceramide clearance via accelerated hydrolysis and glycosylation has been shown to be an element in chemotherapy-resistant AML, a problem considering the crucial role ceramide plays in eliciting apoptosis. Herein we employed agents that block ceramide clearance to determine if such a "reset" would be of therapeutic benefit. SACLAC was utilized to limit ceramide hydrolysis, and D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-threo-PDMP) was used to block the glycosylation route. The SACLAC D-threo-PDMP inhibitor combination was synergistically cytotoxic in drug-resistant, P-glycoprotein-expressing (P-gp) AML but not in wt, P-gp-poor cells. Interestingly, P-gp antagonists that can limit ceramide glycosylation via depression of glucosylceramide transit also synergized with SACLAC, suggesting a paradoxical role for P-gp in the implementation of cell death. Mechanistically, cell death was accompanied by a complete drop in ceramide glycosylation, concomitant, striking increases in all molecular species of ceramide, diminished sphingosine 1-phosphate levels, resounding declines in mitochondrial respiratory kinetics, altered Akt, pGSK-3β, and Mcl-1 expression, and caspase activation. Although ceramide was generated in wt cells upon inhibitor exposure, mitochondrial respiration was not corrupted, suggestive of mitochondrial vulnerability in the drug-resistant phenotype, a potential therapeutic avenue. The inhibitor regimen showed efficacy in an in vivo model and in primary AML cells from patients. These results support the implementation of SL enzyme targeting to limit ceramide clearance as a therapeutic strategy in chemotherapy-resistant AML, inclusive of a novel indication for the use of P-gp antagonists.
    Keywords:  P-glycoprotein; acute myeloid leukemia; ceramide; chemotherapy resistance; sphingolipids
    DOI:  https://doi.org/10.3390/cancers15061883
  9. Exp Hematol. 2023 Mar 29. pii: S0301-472X(23)00157-1. [Epub ahead of print]
    Ex vivo reprogramming of human hematopoietic stem cells is accompanied by increased transcripts of genes regulating metabolic integrity.
    Luena Papa, Tiphaine C Martin, Mansour Djedaini, Mahtab Zangui, Umut Ozbek, Ramon Parsons, Ronald Hoffman, Christoph Schaniel.
      The regenerative potential of human hematopoietic stem cells (HSCs) is functionally defined by their ability to provide life-long blood cell production and to repopulate myeloablated allogeneic transplant recipients. The expansion of HSC numbers is dependent not only on HSC divisions but also on a coordinated adaptation of HSCs to metabolic stress. These variables are especially critical during the ex vivo culture of HSCs with cytokine combinations that frequently results in HSC exhaustion. We have previously reported that human CD34+ hematopoietic stem and progenitor cells (HSPC) can be efficiently reprogrammed ex vivo and that the number of phenotypic HSCs with long-term repopulation capacity is expanded in the presence of a combination of cytokines and an epigenetic modifier. Here, we present evidence that ex vivo HSC reprogramming and maintenance is accompanied by increased transcripts of genes regulating metabolic integrity, including SIRT1 and SIRT3.
    Keywords:  SIRT1/SIRT3; hematopoietic stem cells; metabolic integrity; reprogramming; single-cell CITE-seq
    DOI:  https://doi.org/10.1016/j.exphem.2023.03.006
  10. Metabolites. 2023 Feb 25. pii: 345. [Epub ahead of print]13(3):
    The Role of Reprogrammed Glucose Metabolism in Cancer.
    Meran Keshawa Ediriweera, Sharmila Jayasena.
      Cancer cells reprogram their metabolism to meet biosynthetic needs and to adapt to various microenvironments. Accelerated glycolysis offers proliferative benefits for malignant cells by generating glycolytic products that move into branched pathways to synthesize proteins, fatty acids, nucleotides, and lipids. Notably, reprogrammed glucose metabolism and its associated events support the hallmark features of cancer such as sustained cell proliferation, hijacked apoptosis, invasion, metastasis, and angiogenesis. Overproduced enzymes involved in the committed steps of glycolysis (hexokinase, phosphofructokinase-1, and pyruvate kinase) are promising pharmacological targets for cancer therapeutics. In this review, we summarize the role of reprogrammed glucose metabolism in cancer cells and how it can be manipulated for anti-cancer strategies.
    Keywords:  cancer; cancer treatment; glucose; metabolism
    DOI:  https://doi.org/10.3390/metabo13030345
  11. Int J Mol Sci. 2023 Mar 13. pii: 5493. [Epub ahead of print]24(6):
    Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma.
    Yuyang Pang, Tingxun Lu, Zijun Y Xu-Monette, Ken H Young.
      Lymphoma is a heterogeneous group of diseases that often require their metabolism program to fulfill the demand of cell proliferation. Features of metabolism in lymphoma cells include high glucose uptake, deregulated expression of enzymes related to glycolysis, dual capacity for glycolytic and oxidative metabolism, elevated glutamine metabolism, and fatty acid synthesis. These aberrant metabolic changes lead to tumorigenesis, disease progression, and resistance to lymphoma chemotherapy. This metabolic reprogramming, including glucose, nucleic acid, fatty acid, and amino acid metabolism, is a dynamic process caused not only by genetic and epigenetic changes, but also by changes in the microenvironment affected by viral infections. Notably, some critical metabolic enzymes and metabolites may play vital roles in lymphomagenesis and progression. Recent studies have uncovered that metabolic pathways might have clinical impacts on the diagnosis, characterization, and treatment of lymphoma subtypes. However, determining the clinical relevance of biomarkers and therapeutic targets related to lymphoma metabolism is still challenging. In this review, we systematically summarize current studies on metabolism reprogramming in lymphoma, and we mainly focus on disorders of glucose, amino acids, and lipid metabolisms, as well as dysregulation of molecules in metabolic pathways, oncometabolites, and potential metabolic biomarkers. We then discuss strategies directly or indirectly for those potential therapeutic targets. Finally, we prospect the future directions of lymphoma treatment on metabolic reprogramming.
    Keywords:  lymphoma; metabolism; targeted therapy
    DOI:  https://doi.org/10.3390/ijms24065493
  12. Front Oncol. 2023 ;13 1170115
    Editorial: Hallmark of cancer: Evasion of growth suppressors.
    Christina H Scheel, Reinhold Schäfer.
      
    Keywords:  HADHB gene; INPP4B gene; cancer metabolism; cell death; maspin; post-translational protein modification
    DOI:  https://doi.org/10.3389/fonc.2023.1170115
  13. bioRxiv. 2023 Mar 23. pii: 2023.03.21.533091. [Epub ahead of print]
    Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade.
    Mahnoor Mahmood, Eric Minwei Liu, Amy L Shergold, Elisabetta Tolla, Jacqueline Tait-Mulder, Alejandro Huerta Uribe, Engy Shokry, Alex L Young, Sergio Lilla, Minsoo Kim, Tricia Park, J L Manchon, Crístina Rodríguez-Antona, Rowan C Walters, Roger J Springett, James N Blaza, Sara Zanivan, David Sumpton, Edward W Roberts, Ed Reznik, Payam A Gammage.
      The mitochondrial genome encodes essential machinery for respiration and metabolic homeostasis but is paradoxically among the most common targets of somatic mutation in the cancer genome, with truncating mutations in respiratory complex I genes being most over-represented 1 . While mitochondrial DNA (mtDNA) mutations have been associated with both improved and worsened prognoses in several tumour lineages 1-,3 , whether these mutations are drivers or exert any functional effect on tumour biology remains controversial. Here we discovered that complex I-encoding mtDNA mutations are sufficient to remodel the tumour immune landscape and therapeutic resistance to immune checkpoint blockade. Using mtDNA base editing technology 4 we engineered recurrent truncating mutations in the mtDNA-encoded complex I gene, Mt-Nd5 , into murine models of melanoma. Mechanistically, these mutations promoted utilisation of pyruvate as a terminal electron acceptor and increased glycolytic flux without major effects on oxygen consumption, driven by an over-reduced NAD pool and NADH shuttling between GAPDH and MDH1, mediating a Warburg-like metabolic shift. In turn, without modifying tumour growth, this altered cancer cell-intrinsic metabolism reshaped the tumour microenvironment in both mice and humans, promoting an anti- tumour immune response characterised by loss of resident neutrophils. This subsequently sensitised tumours bearing high mtDNA mutant heteroplasmy to immune checkpoint blockade, with phenocopy of key metabolic changes being sufficient to mediate this effect. Strikingly, patient lesions bearing >50% mtDNA mutation heteroplasmy also demonstrated a >2.5-fold improved response rate to checkpoint inhibitor blockade. Taken together these data nominate mtDNA mutations as functional regulators of cancer metabolism and tumour biology, with potential for therapeutic exploitation and treatment stratification.
    DOI:  https://doi.org/10.1101/2023.03.21.533091
  14. Adv Cancer Res. 2023 ;pii: S0065-230X(22)00091-4. [Epub ahead of print]158 41-71
    Epigenetically programmed resistance to chemo- and immuno-therapies.
    Reddick R Walker, Zainab Rentia, Katherine B Chiappinelli.
      Resistance to cancer treatments remains a major barrier in developing cancer cures. While promising combination chemotherapy treatments and novel immunotherapies have improved patient outcomes, resistance to these treatments remains poorly understood. New insights into the dysregulation of the epigenome show how it promotes tumor growth and resistance to therapy. By altering control of gene expression, tumor cells can evade immune cell recognition, ignore apoptotic cues, and reverse DNA damage induced by chemotherapies. In this chapter, we summarize the data on epigenetic remodeling during cancer progression and treatment that enable cancer cell survival and describe how these epigenetic changes are being targeted clinically to overcome resistance.
    Keywords:  3D chromatin; Acetylation; Cancer; Chemotherapy; Epigenetics; Histone modifications; Immunotherapy; Methylation
    DOI:  https://doi.org/10.1016/bs.acr.2022.12.001
  15. J Family Med Prim Care. 2022 Nov;11(11): 7335-7338
    Utility of Flow Cytometry in Diagnosis of Acute Leukemias: A Study at RIMS, Ranchi, India.
    Sunil K Mahto, Niraj Prasad.
       Introduction: Leukemia is a neoplastic disorder originating in a hematopoietic cell that has undergone an intrinsic change, causing it to escape from the normal restraints imposed on proliferative activity. Immunophenotyping is now the preferred method for diagnosing, classifying, staging and monitoring the disease progression as well as response to therapy.
    Material and Method: The material of the present study consisted of 51 patients suffering from hematological malignancies who attended and /or were admitted in Rajendra Institute of Medical Sciences, Ranchi during the period from March 2018 to August 2019.
    Results: A total of 51 cases were diagnosed as acute leukemia on microscopic examination. On immunophenotyping, 36 cases (70.6%) were diagnosed as Acute Myeloid Leukemia (AML), 15 cases (29.4%) were diagnosed as Acute Lymphoblastic Leukemia (ALL). ALL cases were further divided into B-Cell ALL and T-Cell ALL with 8 cases (15.7%) and 7 cases (13.7%) respectively. Cytogenetics could not be done for these cases due to non-availability of the set-up for the same at the institute.
    Conclusion: Flowcytometry can be a great tool in diagnosis and categorisation of leukemia especially at centres where cytogenetics is not available.
    Keywords:  Flow cytometry; immunophenotyping; leukemia
    DOI:  https://doi.org/10.4103/jfmpc.jfmpc_1211_21
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:10.