A list of recent important research progress on leukemia

1Genetic-transcriptiography analysis identified the key transcription factor as the driver of human red leukemia
acute erytic leukemia (AML-M6 or AEL) is a rare invasive blood tumorPrevious studies have shown that AEL leukemia cells typically carry complex nucleotypes and mutations known to AML-related cancer genesTo better define the potential molecular mechanisms that drive red line phenotypes, the researchers studied 33 AEL sample series representing three genetic subgroups of AEL, including TP53 mutations, epigenetic regulators (such as DNMT3A, TET2, or IDH2), and undefined case loads of low mutationloadsThe researchers created a "space" based on transcriptional strains of red vs myelin, in which most AEL samples showed unique positioning that was different from those of non-M6 AML and bone marrow hyperplasia syndrome samples, independent of the above-mentioned molecular subgroupsNotably, more than 25% of AEL patients showed abnormal expression of key transcription altimeter factors, including SKI, ERG, and ETO2The ectopic expression of these factors in mouse red line precursor cells hinders in vitro differentiation of the red line, leading to eternal dysphochioization, and is related to reduced chromatin accessibility at GATA1 binding sites and functional interference with GATA1 activityInvivia models show that the occurrence of deadly red lines, red lines/myelin hybrids, or other malignancies depends on the cell population that expresses AEL-related mutations2: Low doses of amycin may overcome leukemia resistancethe researchers hypothesized that inhibiting Akt phosphorylation of beta-serial proteins reduces the activity of the former and inhibits leukemiaTo test this hypothesis, the researchers conducted a high-throughput screening of chemical libraries approved by the U.SFood and Drug AdministrationAdministration and theAdministration, and identified 24 lead compounds The researchers used low-dose amycin to treat mice with double mutations, along with the clinically used chemical agent Nairabin They observed that chemotherapy was effective in eliminating the majority of leukemia cells, but induced the amplification of the stem cell that accounted for a small number of leukemia stem cells In contrast, low doses of amycin had no effect on leukemia cells, but reduced leukemia stem cells A combination of low-dose amycin and nairabin therapy worked best To further confirm the inhibitory effect, the researchers collaborated on a small clinical trial to test the response of 10 to 20 patients with acute myeloid leukemia who had become resistant to chemotherapy to jothromycin The results showed that 50% of patients with acute myeloid leukemia who were already resistant to chemotherapy responded to low doses of erythromycin and significantly reduced the number of leukemia stem cells In addition, the study found that low-dose amycin inhibits leukemia stem cells and relies on T-cells that express CD8 against cancer As a result, the new treatment simply targets leukemia stem cells, but also exposes them to activated immune responses PD-1 inhibitor treatment leads to rapid progress iphone ticias tic adult T-cell leukemia/
lymphoma
immunoosinth inhibitors are powerful new tools for treating cancer and can extend the duration of remission for a variety of diseases, including hematologic malignancies such as Hodgkin's lymphoma But in a recent report, Rauch et al found that PD-1 inhibitor navuzumatoscans can lead to rapid progression in adult T-cell leukemia/lymphoma (ATLL) patients The researchers obtained primary cells from patients to study the causes of this malignant advance Analysis of the cloning of malignant cells, somatic cell mutations and gene expression confirmed reports of rapid progression of PD-1 resistance lag in these patients, revealed the origin of these malignant cells, discovered a new link between ATLL cells and intra-tumor regulatory T cells (Tregs), and revealed the anti-cancer effect of PD-1 in ATLL In summary, this study identifies the mechanisms that lead to this amazing result in NAL in Navuspena therapy, or can provide broad reference value for the growing problem of rapid advances in immunootherapy the association between the subclonal NT5C2 mutation and the adverse prognosis after the recurrence of acute lymphoblastic leukemia To test the clinical effect of NT5C2 mutation on PATIENTs with ALL relapse, Malwine J Barz et al used sequencing and sensitive allelin gene specificity RT-PCR to analyze 455 cases of recurrent B-cell precursor ALL5C2 gene treated in ALL-REBF 2002 recurrence trial The researchers detected 110 NT5C2 mutations in 75 patients (75/455, 16.5%) of recurrent B-cell precursor ALL patients Two-thirds of relapsed cases carry sub-clone mutations, and only one-third of relapses carry clone mutations Compared to patients without NT5C2 mutations, patients with NT5C2 cloning and sub-clone mutations had a lower rate of relapse no-event survival However, in multifactoric analysis, the sub-clone NT5C2 mutation was associated with reduced event-free survival and inefficiency in recurrence therapy, while NT5C2 cloned mutation swasated However, 27 of the 33 subclonal NT5C2 mutations (82%) could not be detected without remission or a second relapse, and 10 (71%) of the 14 patients had a subclonal NT5C2 mutation that could no longer be detected after relapse-induced treatment This suggests that the subclonal NT5C2 mutation defines the recurrence associated with the patient's high risk of treatment failure, while emphasizing their complex role in prognosis beyond the range of the mutation NT5C2 as a targeted driver in the recurrence progression Sensitivity to NT5C2 mutations, forward-looking identification helps to improve the understanding and treatment of this invasive ALL recurrence subtype 5) Myc-Miz-1 signal promotes self-renewal of leukemia stem cells by inhibiting the expression of Cebp alpha and Cebp, in most acute myeloid leukemia (AML), c-Myc polyabnormalexpression and/or amplification The proliferation and survival of almost all AML cells depends on Myc MycV394D is a mutant form of Myc that lacks anti-inhibition due to its lack of ability to interact with Miz1 The researchers found that mycV394D had significantly impaired tumor-causing function compared to Myc Compared to mice receiving Myc transduction hematopoietic stem cells (HSPCs), there was a significant delay in the occurrence of AML/bone marrow hyperpluses in mice receiving MycV394D transduction HSPCs Using the MLL-AF9 AML mouse model, the researchers found that partial differentiation of AML cells expressing MycV394D (exhausted endogenous Myc) decreased in vitro colonization and leukemia formation Leukemia stem cells (LSCs) are reduced in proportion to MycV394D-AML cells and their ability to produce leukemia during continuous transplantation, suggesting that Myc-Miz1 interactionise is necessary for LSCs self-renewal In addition, the researchers found that MycV394D-AML cells are more sensitive to chemotherapy than Myc-AML cells In terms of mechanism, Myc plays an important role in the pathogenesis of AML by maintaining the undifferentiated state and self-renewal of LSCs to inhibit the expression of Cebp alpha and Cebp- mediated by Miz1 Source: MedSci Original