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DNA Methylation and Epigenetics: New Developments in Biology and Treatment
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Jesus Duque, Michael Lübbert, Mark Kirschbaum
It thus comes as no surprise that mutations in MLL would be associated with cancer; over 50 mutated fusion proteins as the result of chromosomal translocations have been described, and this mutation is frequent in ALL of infants (90). It is noteworthy that MLL-related transformation, with the resultant disregulation of Hox proteins, is dependent on its association with menin, implicating the methyltransferase activity as critical for leukemogenesis (91,92). It is thus interesting that the “repression domain” of MLL is specific for unmethylated CpG sequences (93).
Precision medicine in acute myeloid leukemia
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
The mixed lineage leukemia gene (MLL, also known as ALL-1 or HRX), located on chromosome 11q23, encodes a histone methyltransferase and is frequently rearranged in AML. Recurrent translocations of MLL are generally considered to confer a poor prognosis (Meyer et al., 2009; Pigneux et al., 2015). Fusion proteins with more than 60 partners were characterized and these partners also have a significant effect on disease outcome (Coenen et al., 2011). Other entities that have been associated with poor prognosis are t(6;9)(p23;q34), t(9;22)(q34;q11), and 17p deletions (Smith et al., 2011).
Reproductive Disorders Associated with Pesticide Exposure
Published in Ana Maria Osorio, Lynn R. Goldman, Proceedings from the Medical Workshop on Pesticide-Related Illnesses from the International Conference on Pesticide Exposure and Health, 2017
Childhood Cancer: Exposure to indoor pesticides during pregnancy doubled the risk for childhood leukemia in a well-designed case-control study in California.58 At the time of the study, the most common home insecticides used in the region were chlorpyrifos, piperonyl butoxide, pyrethrins and propoxur. In a study of 136 cases of infant leukemia and 266 controls, having an affected child was associated with maternal exposure to pesticides during pregnancy, particularly the carbamate, propoxur.59 The finding was most striking among infants with cleavage of the mixed lineage leukemia (MLL) gene, which is a known mechanism of leukemia induction after treatment with anti-neoplastic drugs or radiation. A case of infant leukemia with MLL gene rearrangement has also been reported after intensive exposure to permethrin during pregnancy.60
Menin-MLL protein-protein interaction inhibitors: a patent review (2014–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Huanrong Bai, San-Qi Zhang, Hao Lei, Fang Wang, Mengyan Ma, Minhang Xin
The mixed lineage leukemia (MLL, also known as KMT2A, MLL1) protein is a kind of histone methyltransferases, which is targeted by chromosomal translocations and rearrangements in the acute leukemia (AL) observed in approximately 10% of human leukemia patients [1–3]. The oncogenic activity of MLL fusion proteins depends on the direct interaction with the Menin protein, which is a tumor suppressor controlling the cellular growth in the endocrine organs [4–6]. Studies have shown that the binding of Menin to the N-terminal motif of the MLL fusion protein is essential for MLL fusion acute leukemia [7–9]. Therefore, inhibition of the Menin-MLL protein-protein interactions is considered as a therapeutic strategy for relapsed or refractory AL, such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and phenotypic leukemia.
Hsa-circ_0003420 induces apoptosis in acute myeloid leukemia stem cells and impairs stem cell properties
Published in Immunopharmacology and Immunotoxicology, 2021
Guoqiang Lin, Yingying Fei, Yanming Zhang
AML is a markedly heterogeneous and invasive malignant tumor that forms pre-LSC clones through a series of events, such as repeated mutation and fusion of the MLL gene, that leads to an abnormal program of self-renewal and supplies a selective growth advantage relative to the original cell population, ultimately resulting in cancer [18]. Each pre-LSC undergoes different additional cooperation event(s), providing pre-LSCs an opportunity to further transform into a heterogeneous LSC pool with enhanced self-renewal activities [19,20]. Given that persistent LSCs are the main cause of treatment failure and recurrence in the case of some aggressive AML subtypes, it is critical to investigate the transformation process and molecular pathways involved in maintaining the LSC pool to create effective cancer treatment strategies. Our study revealed that compared to healthy CD34 + CD38− cells, hsa-circ_0003420 expression was inhibited in LSCs and AML CD34 + CD38− cells. The inhibition of hsa-circ_0003420 expression was also associated with poor clinical outcomes and reduced curative effects in AML patients, indicating that hsa-circ_0003420 expression in LSCs might be a promising prognostic signal of clinical outcomes for AML.
Morel-Lavallée lesions (internal degloving injuries) of the lower extremity in the pediatric and adolescent population
Published in The Physician and Sportsmedicine, 2021
Indranil Kushare, Ramesh Babu Ghanta, Nicole A. Wunderlich
Pediatric patients in our study were successfully treated with non-operative or minimally invasive procedures, which is in contrast to adult MLLs which are predominantly treated with intervention. Referrals were required for various specialists like plastic surgery and interventional radiology [7,19,27–30]. Historically, a multitude of treatment modalities have been used for management such as compression therapy/bandaging, percutaneous aspiration, sclerosant injection, doxycycline sclerodesis, pulse lavage, and open debridement which have all been utilized for management of MLL injuries [5,7,8,10,11,18,19,27,28,30]. These potential options for referral should be kept in mind by the primary care physicians who see these injuries at presentation for appropriate referrals as deemed necessary. The conservative management in our young patients is in line with case reports and literature treating MLL in athletes and younger patients [11–13]. On the other hand, our hip/thigh MLLs patient cohort needed slightly more intervention like the adult counterparts in literature where surgery is mainstay of treatment [9,10,19,30].