健康な個体における急性骨髄性白血病リスクの予測

Sagi Abelson¹, Grace Collord^2,3, Stanley W K Ng⁴

¹Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada.

Nature

|July 11, 2018

まとめ

研究者らは,白血病前変異と良性年齢関連のクローン細胞形成を区別するために深層配列化を用いたモデルを開発し,診断の数年前に急性骨髄性白血病 (AML) のリスクの早期発見を可能にしました.

科学分野:

血液学
腫瘍学
遺伝学

背景:

急性骨髄白血病 (AML) の発生率と死亡率は年齢とともに増加し,しばしば骨髄不全を示します.
De novo AMLは,血液生成幹細胞と前身細胞 (HSPC) の体内の変異によって生じるが,同様の変異は,健康な老化している個体でも発生する (年齢関連のクローン血液形成,ARCH).
前白血病のARCHと良性のARCHを区別することは,早期のAMLリスク評価において極めて重要です.

研究の目的:

高リスクの白血病前変異と良性年齢関連のクローナル血液形成 (ARCH) を,ディープシーケンシングを用いて区別する.
急性骨髄性白血病 (AML) の生存率を予測するモデルを開発する.
予測モデルを独立したコホートと電子医療記録で検証する.

主な方法:

AML以前の症例と年齢/性別を合わせた対照群の周辺血液細胞の深層配列化
変異負荷,変異アレル頻度,遺伝子変異濃縮の分析
遺伝子パラメータと電子医療記録を用いた,AMLフリー生存率とAMLリスクの予測モデルの開発と検証

主要な成果:

AML以前の症例は,サンプル毎の変異が著しく多く,対照群と比較してより高い変異アレル頻度を示した.
特定の遺伝子変異はAML以前のグループで濃縮され,より大きなクローン拡張を示しました.
派生したモデルは,AMLの生存率を正確に予測し,AMLのリスクが高い個人を特定しました.

結論:

良性年齢関連のクローナル血液形成 (ARCH) と,悪性変異の何年も前の白血病前状態を区別することが可能である.
この差別により,急性骨髄性白血病 (AML) のリスクが高い個人を早期に発見し,モニタリングし,潜在的な介入が可能になります.
この発見は,AMLリスクの早期分層化のための概念の証明を提供します.

さらに関連する動画

10:02

Intra-Peritoneal Transplantation for Generating Acute Myeloid Leukemia in Mice

Published on: January 6, 2023

2.5K

06:33

Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies

Published on: November 10, 2023

1.9K

関連する概念動画

02:27

Predicting Molecular Geometry

46.0K

VSEPR Theory for Determination of Electron Pair Geometries

46.0K

01:30

Impact of Individuals on Individuals

403

Human behavior is intricately shaped by social influences that arise from interactions with others in diverse contexts. These influences not only mold beliefs and attitudes but also drive the regulation of behaviors through both direct communication and observational learning. The study of these processes falls within the domain of social psychology, which seeks to understand how individuals are affected by and affect those around them.Mechanisms of Social InfluenceDirect social influence...

403

01:12

Relative Risk

2.2K

Relative risk (RR) is a statistical measure commonly used in epidemiology to compare the likelihood of a particular event occurring between two groups. This metric is important for evaluating the relationship between exposure to a specific risk factor and the probability of a particular outcome. It plays a crucial role in medical research, public health studies, and risk assessment. Relative risk quantifies how much more (or less) likely an event is to occur in an exposed group compared to an...

2.2K

01:03

Prediction Intervals

3.4K

The interval estimate of any variable is known as the prediction interval. It helps decide if a point estimate is dependable.
However, the point estimate is most likely not the exact value of the population parameter, but close to it. After calculating point estimates, we construct interval estimates, called confidence intervals or prediction intervals. This prediction interval comprises a range of values unlike the point estimate and is a better predictor of the observed sample value, y.

3.4K

01:26

Factors Affecting the Risk of Infection

13.7K

The hosts' susceptibility to infection depends on several factors. The integrity of the skin and mucous membranes helps protect the body against microbial attacks. When the skin is altered, the chance of infection, limb loss, and even death increases.
The integrity and count of the white blood cells help the body resist pathogens and fight infection. When impaired, it reduces the body's resistance to pathogens. The acidic pH levels of the gastrointestinal, genitourinary tracts, and skin...

13.7K

01:07

End Point Prediction: Gran Plot

1.2K

A Gran plot is used to predict the equivalence volume or endpoint of a potentiometric or acid-base titration without reaching the endpoint. Typically, titration data is collected as a function of the titrant's volume up to a point less than the equivalence volume and then transformed into a linear format. The straight line is extended to the x-axis, indicating the necessary titrant volume to achieve the equivalence point.
For potentiometric titration, the Gran plot is created by plotting...