- Synthetic lethal targeting of TET2-mutant haematopoietic stem and progenitor cells by XPO1 inhibitors. [Journal Article]Br J Haematol. 2023 Feb 06 [Online ahead of print]BJ
- TET2 inactivating mutations serve as initiating genetic lesions in the transformation of haematopoietic stem and progenitor cells (HSPCs). In this study, we analysed known drugs in zebrafish embryos for their ability to selectively kill tet2-mutant HSPCs in vivo. We found that the exportin 1 (XPO1) inhibitors, selinexor and eltanexor, selectively kill tet2-mutant HSPCs. In serial replating colony…
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- High Expression of CD300A Predicts Poor Survival in Acute Myeloid Leukemia. [Journal Article]Acta Haematol. 2023 Feb 06 [Online ahead of print]AH
- CONCLUSIONS: The expression levels of CD300A were associated with risk stratification and the clinical relevance of AML. High CD300A expression may act as an independent adverse prognostic factor for OS and RFS in AML.
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- TIM-3 signaling hijacks the canonical Wnt/β-catenin pathway to maintain cancer stemness in acute myeloid leukemia. [Journal Article]Blood Adv. 2023 Feb 06 [Online ahead of print]BA
- The activation of β-catenin plays critical roles in normal stem cell function, and when aberrantly activated, maintenance and enhancement of cancer stemness in many solid cancers. The aberrant β-catenin activation is also observed in acute myeloid leukemia (AML), and crucially contributes to self-renewal and propagation of leukemic stem cells (LSCs) regardless of mutations in contrast to such sol…
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- Venetoclax in combination with hypomethylating agent for the treatment of advanced myeloproliferative neoplasms and acute myeloid leukemia with extramedullary disease. [Journal Article]Leuk Lymphoma. 2023 Feb 06 [Online ahead of print]LL
- The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic…
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- A potential area of use for immune checkpoint inhibitors: Targeting bone marrow microenvironment in acute myeloid leukemia. [Review]Front Immunol. 2023; 14:1108200.FI
- Acute myeloid leukemia (AML) arises from the cells of myeloid lineage and is the most frequent leukemia type in adulthood accounting for about 80% of all cases. The most common treatment strategy for the treatment of AML includes chemotherapy, in rare cases radiotherapy and stem cell and bone marrow transplantation are considered. Immune checkpoint proteins involve in the negative regulation of i…
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- A comprehensive analysis of cytogenetics, molecular profile, and survival among pediatric acute myeloid leukemia: a prospective study from a tertiary referral center. [Journal Article]Am J Blood Res. 2022; 12(6):177-189.AJ
- CONCLUSIONS: The majority of patients had abnormal/recurrent cytogenetics abnormalities. FAB M2 subtype showed frequent aberrant expression of the CD19. The absence of molecular markers may suggest the presence of CD7, CD11b, and CD36a expression. The overall survival has increased considerably in LMIC.
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- Immune therapy: a new therapy for acute myeloid leukemia. [Review]Blood Sci. 2023 Jan; 5(1):15-24.BS
- Although complete remission could be achieved in about 60%-70% of acute myeloid leukemia (AML) patients after conventional chemotherapy, relapse and the state of being refractory to treatment remain the main cause of death. In addition, there is a great need for less intensive regimens for all medically frail patients (both due to age/comorbidity and treatment-related). Immune therapy anticipates…
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- Renal Angiomyolipoma Causing Inferior Vena Cava Thrombus in a Young Girl With Tuberous Sclerosis. [Case Reports]Cureus. 2023 Jan; 15(1):e33244.C
- Angiomyolipomas (AML), also known as hamartomas, are benign mesenchymal tumors of the kidneys which consist of vascular tissue, smooth muscles, and adipose tissue, with a higher prevalence in females than males. AML may be associated with tuberous sclerosis, and the growth of the mass may present as hematuria or flank pain. We present a case of a 14-year-old female patient who had a known case of…
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- High-expression of the innate-immune related gene UNC93B1 predicts inferior outcomes in acute myeloid leukemia. [Journal Article]Front Genet. 2023; 14:1063227.FG
- Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with dismal prognosis. Identification of better biomarkers remained a priority to improve established stratification and guide therapeutic decisions. Therefore, we extracted the RNA sequence data and clinical characteristics of AML from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression database (GTEx) to identify…
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- Editorial: Uncovering the relationship between myelodysplastic syndromes and acute myeloid leukemia. [Editorial]Front Oncol. 2023; 13:1131785.FO
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- Verbenalin attenuates hepatic damage and mitochondrial dysfunction in alcohol-associated steatohepatitis by regulating MDMX/PPARα-mediated ferroptosis. [Journal Article]J Ethnopharmacol. 2023 Feb 03 [Online ahead of print]JE
- CONCLUSIONS: Verbenalin regulates ferroptosis and highlights the therapeutic potential of verbenalin and ferroptosis inhibition in reducing alcoholic steatohepatitis.
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- Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia. [Journal Article]Oncogene. 2023 Feb 04 [Online ahead of print]O
- Isocitrate dehydrogenase 2 (IDH2) mutations occur in more than 15% of cytogenetically normal acute myeloid leukemia (CN-AML) but comparative studies of their roles in leukemogenesis have been scarce. We generated zebrafish models of IDH2R172K and IDH2R140Q AML and reported their pathologic, functional and transcriptomic features and therapeutic responses to target therapies. Transgenic embryos co…
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- Mitochondrial fusion is a therapeutic vulnerability of acute myeloid leukemia. [Journal Article]Leukemia. 2023 Feb 04 [Online ahead of print]L
- Mitochondrial metabolism recently emerged as a critical dependency in acute myeloid leukemia (AML). The shape of mitochondria is tightly regulated by dynamin GTPase proteins, which drive opposing fusion and fission forces to consistently adapt bioenergetics to the cellular context. Here, we showed that targeting mitochondrial fusion was a new vulnerability of AML cells, when assayed in patient-de…
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- Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia. [Journal Article]Leukemia. 2023 Feb 04 [Online ahead of print]L
- Murine models offer a valuable tool to recapitulate genetically defined subtypes of AML, and to assess the potential of compound mutations and clonal evolution during disease progression. This is of particular importance for difficult to treat leukemias such as FLT3 internal tandem duplication (ITD) positive AML. While conditional gene targeting by Cre recombinase is a powerful technology that ha…
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- The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors. [Journal Article]
- Acute myeloid leukemia (AML) patients with FLT3-ITD mutations are associated with poor prognosis. FLT3-ITD inhibitors are developed and result in transient disease remission, but generally resistance develops. We propose that resistance occurs due to apoptosis evasion. We compared the abilities of five clinically used FLT3-ITD inhibitors, namely, midostaurin, crenolanib, gilteritinib, quizartinib…
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- mRNA-lncRNA gene expression signature for predicting pediatric AML relapse. [Journal Article]Curr Res Transl Med. 2023 Jan 25; 71(2):103379.CR
- Children with acute myeloid leukemia (AML) face a relapse of the disease in 30% of all cases. AML relapse is difficult to predict, and existing risk scales are often ineffective. Using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET-AML) project, we defined an expression signature based on matrix RNAs (mRNAs) and long non-coding RNAs (lncRNAs) that could…
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- Correlation of blood cell counts with mutant subtypes and impact prognosis in acute myeloid leukemia patients with FLT3 mutations. [Journal Article]Hematology. 2023 Dec; 28(1):2172296.H
- CONCLUSIONS: In AML patients with FLT3 mutations, the location of FLT3 mutations and the type of co-mutated genes may be correlated with blood cell counts, and different blood cell counts may have an impact on the prognosis.
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- Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia. [Journal Article]
- CONCLUSIONS: Collectively, we constructed a prediction model based on seven cuproptosis-related lncRNAs for AML prognosis. The obtained risk score may reveal the immunotherapy response in patients with this disease.
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- Acetylation stabilizes the signaling protein WISP2 by preventing its degradation to suppress the progression of acute myeloid leukemia. [Journal Article]J Biol Chem. 2023 Jan 31 [Online ahead of print]JB
- Acute myeloid leukemia (AML) is challenging to treat due to its heterogeneity, prompting a deep understanding of its pathogenesis mechanisms, diagnosis, and treatment. Here, we found reduced expression and acetylation levels of WISP2 in bone marrow mesenchymal stem cells (BMMCs) from AML patients and that AML patients with lower WISP2 expression tended to have reduced survival. At the functional …
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- Discovery of novel and bioavailable histone deacetylases and cyclin-dependent kinases dual inhibitor to impair the stemness of leukemia cells. [Journal Article]Eur J Med Chem. 2023 Jan 21; 249:115140.EJ
- Acute myeloid leukemia (AML) has been confirmed as one of the most lethal heterogeneous clonal diseases. In addition to being essential for the development and progression of leukemia, leukemic stem cells (LSCs), a subpopulation of leukemia cells with stem cell characteristics, are also primarily responsible for the development of leukemia relapse and drug resistance. Elimination of stemness and …
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- Discovery of a Potent and Selective STAT5 PROTAC Degrader with Strong Antitumor Activity In Vivo in Acute Myeloid Leukemia. [Journal Article]J Med Chem. 2023 Feb 03 [Online ahead of print]JM
- STAT5 is an attractive therapeutic target for human cancers. We report herein the discovery of a potent and selective STAT5 degrader with strong antitumor activity in vivo. We first obtained small-molecule ligands with sub-micromolar to low micromolar binding affinities to STAT5 and STAT6 SH2 domains and determined co-crystal structures of three such ligands in complex with STAT5A. We successfull…
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- Specific subtype distribution with impact on prognosis of TP53 single hit and double hit events in AML and MDS. [Journal Article]Blood Adv. 2023 Feb 03 [Online ahead of print]BA
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- Rare Pattern of Myelodysplastic Syndrome (MDS) with Serum Monoclonal Immunoglobulin: Case Report. [Journal Article]Altern Ther Health Med. 2023 Feb 03 [Online ahead of print]AT
- CONCLUSIONS: The combination of plasma cell disease and myeloid malignancy may increase mortality. This is uncommon and may be easily misdiagnosed if not detected early. When a myeloid neoplasm tests positive for MDS and serum M protein, clinicians should evaluate for other plasma cell disease.
- Molecular genetics and management of world health organization defined atypical chronic myeloid leukemia. [Journal Article]Ann Hematol. 2023 Feb 03 [Online ahead of print]AH
- Atypical chronic myeloid leukemia (CML) is a rare BCR::ABL1-negative hematopoietic stem cell disease characterized by granulocytic proliferation and granulocytic dysplasia. Due to both the challenging diagnosis and the rarity of atypical CML, comprehensive molecular annotation-based analyses of this disease population have been scarce, and it is currently difficult to identify the optimal treatme…
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- Oncoproteomic profiling of AML: Moving beyond genomics. [Editorial]Expert Rev Proteomics. 2023 Feb 03 [Online ahead of print]ER
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- Efficacy and safety of single pill combination of amlodipine and valsartan in hypertensive Saudi patients. [Journal Article]Eur Rev Med Pharmacol Sci. 2023 Jan; 27(2):773-786.ER
- CONCLUSIONS: Aml/Val SPC therapy effectively lowered BP and had few side effects while being well-tolerated in people with hypertension.
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- Younger Haploidentical Donor Versus Older Matched Unrelated Donor for Patients With AML/MDS. [Journal Article]Am J Hematol. 2023 Feb 02 [Online ahead of print]AJ
- Optimal donor selection is fundamental to successful allogeneic hematopoietic cell transplantation (HCT), and donor age influences survival after both matched unrelated donor (MUD) and haploidentical donor HCT. Though recent studies have shown similar outcomes between MUD and haploidentical HCT, it is unknown if outcomes differ following HCT with younger haploidentical donors compared to HCT with…
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- Mutational Profile, Outcomes, and Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia and Inconclusive Cytogenetic Analysis. [Journal Article]Eur J Haematol. 2023 Feb 02 [Online ahead of print]EJ
- CONCLUSIONS: Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.
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- Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States. [Journal Article]Ann Hematol. 2023 Feb 03 [Online ahead of print]AH
- Intensive chemotherapy (IC) is commonly used to achieve remission in patients with acute myeloid leukemia (AML). Venetoclax plus azacitidine (VEN-AZA) is FDA-approved to treat patients with AML aged ≥ 75 years or who are ineligible for IC. This retrospective analysis used de-identified electronic health records from the US-based Flatiron Health database from patients diagnosed 11/21/2018 to 10/31…
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- A CT-based radiomics nomogram for differentiation of benign and malignant small renal masses (≤4 cm). [Journal Article]Transl Oncol. 2023 Mar; 29:101627.TO
- CONCLUSIONS: The logistic regression model has better discriminative performance than the decision tree model, and the radiomics nomogram based on Rad-score of three-phase joint and clinical factors has a good predictive effect in differentiating benign from malignant of SRM, which may help clinicians develop accurate and individualized treatment strategies.
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