Minimal Residue of Leukemic Stem Cells and Therapeutic Resistance in Acute Myeloid Leukemia

Abstract

Acute Myeloid Leukemia (AML) is characterized by the clonal growth of undifferentiated myeloma progenitor cells, which leads to hematopoiesis and bone marrow failure (Figure 1) [1]. Even though most newly diagnosed AML patients attain morphological full remission following aggressive induction treatment, recurrence rates remain substantial [2]. Cancer is caused by somatically acquired driver mutations, which account for the biological and clinical complexity of diseases. Cancer categorization based on cause is expected to be robust, repeatable, and therapeutically meaningful. This is already visible in AML, where a progressive transition from a morphological categorization system to one that informs causal genetic mutations has occurred [3]. The cause of recurrence has been discovered as treatmentresistant leukemia cells comprising leukemia stem cells (LSCs), known as a minimal residual disease (MRD). Relapse is induced by treatmentresistant leukemia cells with unique gene expression profiles linked with stem less, according to the notion of cancer stem cells [4]. When these drug-resistant cells are detected early, patients can be assigned to salvage therapy or clinical trials before their AML relapses. The idea of identifying molecular MRD after therapy to predict disease relapse in AML patients has been examined, although molecular MRD evaluation is not extensively used in clinical practice. Next-generation sequencing frequently enables the thorough and simultaneous identification of patient-specific somatic mutations during diagnosis and treatment [5]. AML has developed as a complicated, dynamic disease because of whole genome sequencing. There are multiple leukemia genes, most of which are seldom altered, and patients frequently have more than one driver mutation [6]. Many competing clones coexist at any given moment while the disease progresses [7,8]. These findings demonstrate the biological intricacy of AML, although it is unclear how they may impact clinical management. For patients diagnosed with AML, who are 75 years of age or have comorbidities that prevent the administration of traditional intensive chemotherapy, durable remission was shown in the phase III clinical study. The combination of venetoclax and the hyperventilating drug azacitidine has become the standard treatment. Even following therapy with a hyperventilating drug, older people with AML have a dismal prognosis. Azacitidine in combination with venetoclax has demonstrated potential effectiveness. The investigation of leukemia genes in three clinical trials of intense AML treatment, with the recognition that the AML landscape of older individuals may be underrepresented. The structure of driver mutations indicates non-overlapping patient categories, allowing for comprehensive genomic categorization of AML. In contrast to the subclass, we will investigate gene and gene occurrence patterns, as well as how so compound genotypes relate to clinical outcomes. Azacitidinevenetoclax, decitabine-venetoclax, and low-dose cytarabine-venetoclax are currently conventional treatments for elderly or physically impaired patients diagnosed with AML. Even though these combinations are often utilized in patients with relapsed or refractory AML (RR-AML), clinical and genetic determinants of response and survival in RR-AML were shown to be 2%. The total response rate, including morphological leukemia-free status, was 31%. When azacytidine-venetoclax was used instead of low-dose cytarabine-venetoclax, the response rate was greater (9% vs. 15%; P= 0.008). NPM1 mutations were related to better response rates, whereas TP53, KRAS/NRAS, and SF3B1 mutations were associated with poor overall survival. Several processes determine the reference phenotypic expression and its plasticity, as well as the genetic modifications and gene mutations that influence it. In many metabolic and gene expression patterns that make up the patient’s remarkable heterogeneity of leukemia cells. The interplay between leukemia cells. and extra-tumor factors known as the tumor microenvironment adds to the complication [9].