Acute lymphocytic leukemia (ALL) is a blood cancer that starts from the bone marrow that grows rapidly if untreated. It mainly affects children, but can also occur in adults, where the results are usually less favorable. Overall, the body makes too many immature white blood cells called lymphoblasts, which squeeze out healthy cells and destroy normal blood function. Over time, it spreads to organs such as the brain, liver, and spleen. Thanks to research advances, treatment has improved, but challenges such as relapse and treatment side effects remain. In this post, we will explore what makes everything so complicated.
introduce
Acute lymphocytic leukemia (ALL) is an aggressive hematologic malignant tumor characterized by clonal proliferation of immature lymphatic precursors or lymphocytes in the bone marrow, blood, and other organs. Although primarily pediatric cancer with a peak incidence between 2 and 5 years of age, all children affect adults and present unique challenges across age groups.
For researchers and trainees in the field of biomedical sciences, understanding the molecular and cellular mechanisms of all is fundamental, and it is contributing to the ongoing advancement in diagnosis, risk stratification and treatment. This article provides a research-centric overview of all people focusing on pathogenesis, classification, and evolving therapeutic strategies.
Pathogenesis and cell source
All of these are derived from lymphoid progenitors in the bone marrow that obtain genetic and epigenetic changes that disrupt normal differentiation and promote uncontrolled proliferation. These cells may be committed to B cells or T cells Descendant, B-all is the main subtype among children, while T-All is more frequent in adolescents and young people.
Molecular changes usually involve:
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Transcription factor disorder (For example, PAX5,,,,, ikzf1,,,,, ETV6)
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Abnormal kinase signaling (For example, ABL1,,,,, JAK2,,,,, flt3)
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Chromosomal translocation (For example, t(12; 21)[ETV6-RUNX1],,,,, t(9; 22)[BCR-ABL1])
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Copy number exception (For example, delete CDKN2A,,,,, ikzf1)
These mutations promote leukemia by enhancing self-renewal, impairing cell apoptosis and blocking differentiation. In T-ALL, activate Notch1 way is a central carcinogenic event that is observed in more than 50% of cases.
Epidemiology and risk factors
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Incidence: ~ 4,000 new cases per year in the United States
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Age distribution: Shuangfeng Peak – Children (2-5 years old) and elderly people (> 50 years old)
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gender: Slight male advantage
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Race: The incidence rate is higher in white people
Known risk factors
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Genetic syndrome: Trisome 21 (Down syndrome), Bloom syndrome, trigger telangiectia, Fanconi anemia, Li-Fraumeni syndrome
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High dose radiation exposure
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Previous chemotherapy (alkinetic agents, topoisomerase inhibitors)
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DNA repair or genetic mutations in cell cycle genes
Classification and molecular subtypes
WHO Classification in 2022:
B-lymphocytic leukemia/lymphoma (B-ALL):
T-lymphocytic leukemia/lymphoma (T-ALL):
Now, molecular analysis is critical not only for diagnosis, but also for determining the targets that can work (e.g., ABL-level fusion, JAK-STAT activation, CRLF2 rearrangement).
Clinical manifestations
Symptoms are caused by bone marrow failure, leukemia infiltration and metabolic disorders:
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Bone marrow failure: anemia, thrombocytopenia, neutropenia → fatigue, bleeding, infection
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Organ infiltration: Swelling of the liver and adrenal glands, enlarged lymph nodes, and bone pain
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Central nervous system participation: Headache, vomiting, cranial nerve paralysis
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metabolism: Hyperurea, hyperkalemia, tumor lysis syndrome
These nonspecific symptoms often mimic viral infections or autoimmune diseases and require rapid hematological evaluation.
Diagnosis and examination
Preliminary assessment:
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CBC and peripheral smears: Elevated WBC with lymphocytes, anemia, thrombocytopenia
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Bone marrow aspiration/biopsy: ≥20% of lymphocytes define all (each person)
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Flow cytometry: Immunophenotypes used to classify B- and T-Linege and maturation stages
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Cytogenetics/fish: Translocation detection (e.g. t(9; 22),,,,, t(4; 11))
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Molecular assay: RT-PCR or NGS detection fusion transcript or mutation
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Waist pants: Assessing CNS participation
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MRD Assessment: Measurement after induction by flow cytometry or QPCR
Minimum residual disease (MRD) is now a cornerstone biomarker for therapeutic response and risk stratification.
Treatment Overview
1. Induction phase (~4 weeks)
Goal: To achieve complete remission (CR) by eliminating >99% of leukemia cells
Drugs: vincristine, corticosteroids, l-asparaginase, ± phthalate
CNS prevention begins with intrathecal methotrexate/cellular protease
2. Merger/Strength Stage
Goal: Eliminate residual disease and prevent systemic/central nervous system recurrence
Includes high dose methotrexate, cell arabinoid and further intrathecal chemotherapy
3. Maintenance phase (2-3 years)
Target: Suppress late cloning
Daily 6-hydroxytopurine, weekly methotrexate, periodic vincristine/steroid
4. Central nervous system prevention
Universal, given the high risk of central nervous system recurrence. Intrathecal chemical mass radiation may be involved (in some high-risk cases)
Targeted and immunotherapy
Tyrosine kinase inhibitor (TKI)
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for pH+all: Imatinib or dasatinib with chemotherapy significantly improves prognosis
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Newer TKIs used in T315i mutation cases (e.g. Ponatinib)
CAR-T cell therapy
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CD19-oriented CAR-T (e.g., Tisagenlecleucel) achieves re-recovery of MRD-negative in relapsed/refractory B-ALL
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Major adverse reactions: cytokine release syndrome (CRS), immune effector cell-related neurotoxic syndrome (ICANS)
Bispecific T cell Endagers (bite)
Antibody – Drug Conjugate
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Inotuzumab Ozogamicin: Anti-CD22 ADC for relapse/refractory B-ALL
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Related to intravenous dental diseases, especially after transplantation
JAK-STAT pathway inhibition
Prognostic factors
favorable:
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Ages 1-10 years old
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WBC
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High diploid body
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ETV6-RUNX1 Fusion
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Quick MRD clearance
unfavorable:
MRD negative (
Challenges and emerging directions in research
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Relapse/refractory Still a major obstacle; molecular spectrum analysis guides salvage strategies.
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Lineage plasticity and antigen escapes (e.g., CAR-T after CD19 loss) pose therapeutic challenges.
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Cloning evolution Under selective pressure, therapies emphasize the need for longitudinal genome monitoring.
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Improved results in adult and high-risk subgroups (e.g., T-All, lower diploid B-ALL) requires further translational research.
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Epigenetic disorders (For example, Creb,,,,, NSD2) and Metabolic vulnerability Provide potential new goals.
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Next-generation immunotherapy (e.g., specific antibodies, dual-target cars) are in early clinical development.
in conclusion
Acute lymphocytic leukemia is a model disease that understands clonal evolution, targeted therapy and immuno-oncology. Despite significant improvements in childhood survival, the adult population and recurrent disease still have unmet needs. As research continues to dissect genetic, epigenetics and microenvironment drivers for all, future therapies may become increasingly personalized.
For medical research trainees, all provide a rich research platform – spanning stem cell biology, immunotherapy, systemic genomics, and drug resistance. Continuing collaboration between clinicians and scientists is critical to improving outcomes for all patients affected by this aggressive leukemia.
