2024年4月12日发(作者：)

急性淋巴细胞白血病的分子诊断和治疗研究

Acute Lymphoblastic Leukemia Research from Molecular

Diagnosis to Treatment Options

Abstract:

Acute lymphoblastic leukemia (ALL) is the most common

hematological malignancy in children and remains a significant

cause of morbidity and mortality in adults. The molecular

diagnosis of ALL provides a precise understanding of the

heterogeneous nature of the disease and helps to identify high-risk

patients who require intensive treatment. Several molecular

abnormalities have been identified, including mutations in

leukemia-associated genes, chromosomal translocations, and gene

fusions. These molecular alterations provide opportunities for the

development of targeted therapies that can improve patients'

outcomes. This review provides an overview of molecular

diagnostic techniques and emerging targeted therapies that have

shown promising results in the treatment of ALL.

Keywords: Acute lymphoblastic leukemia, Molecular diagnosis,

Targeted therapy, Chromosomal translocations, Gene fusions

Introduction

Acute lymphoblastic leukemia (ALL) is a hematological

malignancy characterized by the proliferation of immature

lymphoid cells in the bone marrow, leading to the infiltration of

other organs. ALL is the most common cancer in children,

accounting for approximately 30% of all childhood malignancies

worldwide. In adults, ALL is a rare disease accounting for only 20%

of all leukemias. However, it remains a significant cause of

morbidity and mortality, particularly in patients with relapsed or

refractory disease. The prognosis of ALL is influenced by several

factors, including age, initial response to therapy, and the presence

of specific genetic abnormalities. The development of molecular

diagnostic techniques has led to a better understanding of the

molecular heterogeneity of ALL and has paved the way for the

development of targeted therapies.

Molecular diagnosis of ALL

The diagnosis of ALL is based on the presence of blast cells in the

bone marrow or peripheral blood, along with clinical

manifestations. Molecular diagnosis techniques have been

developed to provide a better understanding of the molecular basis

of the disease and to identify high-risk patients who require

aggressive treatment. These techniques include cytogenetic

analysis, fluorescence in situ hybridization (FISH), polymerase

chain reaction (PCR), and next-generation sequencing (NGS).

Cytogenetic analysis is a classical technique that involves the

visualization of chromosomal abnormalities using banding

techniques. Chromosomal translocations involving the

immunoglobulin and T-cell receptor genes are common in ALL

and are associated with specific subtypes of the disease. For

example, the t(9;22) Philadelphia chromosome is present in

approximately 25% of adult ALL cases and is associated with a

poor prognosis. FISH is a more sensitive technique that allows the

detection of chromosomal translocations, gene fusions, and copy

number variations using fluorescent probes. PCR is a highly

sensitive technique that amplifies specific DNA sequences and is

widely used to detect fusion genes and minimal residual disease