Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct
Yusuke Hara1,2,3, Norio Shiba2,3,4, Genki Yamato1,2,3
1Department of Paediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan.
Insights
Young children under 3 years old with acute myeloid leukemia (AML) form a distinct subgroup with specific genetic features. Certain genetic markers, like KMT2A-rearrangement, show age-dependent prognostic significance in pediatric AML.
Area of Science:
- Pediatric Oncology
- Hematology
- Molecular Genetics
Background:
- Infants (<1 year) with acute myeloid leukemia (AML) have unique characteristics and chemotherapy vulnerability.
- Children aged 1-2 years may share similarities with infants, necessitating a broader definition of
- younger
- pediatric AML patients.
Purpose of the Study:
- To identify distinct characteristics and prognostic markers in pediatric AML patients younger than 3 years.
- To analyze the impact of specific genetic rearrangements on outcomes in this younger subgroup.
Main Methods:
- Analysis of 723 pediatric AML patients from Japanese AML99 and AML-05 trials.
- Identification of a distinct subgroup aged <3 years.
- Prognostic analysis of genetic markers including KMT2A-rearrangement, CBFA2T3-GLIS2, CBFB-MYH11, and NUP98-KDM5A.
Main Results:
- Patients <3 years were characterized as a distinct subgroup.
- KMT2A-rearrangement, CBFA2T3-GLIS2, CBFB-MYH11, and NUP98-KDM5A were frequently observed in the younger group.
- CBFA2T3-GLIS2 and NUP98-KDM5A were associated with poor survival outcomes (OS, EFS, CIR).
- KMT2A-R showed better prognosis in the younger group, while CBFB-MYH11 showed poorer prognosis compared to older children.
- Age-specific prognostic value of KMT2A-R and CBFB-MYH11 was identified.
Conclusions:
- Pediatric AML patients <3 years constitute a distinct subgroup with unique genetic profiles.
- Specific molecular markers (CBFA2T3-GLIS2, NUP98-KDM5A) are linked to poor prognoses in this young group.
- The prognostic impact of certain genetic markers (KMT2A-R, CBFB-MYH11) varies significantly with age in pediatric AML.
Abstract:
Although infants (age <1 year) with acute myeloid leukaemia (AML) have unique characteristics and are vulnerable to chemotherapy, children aged 1-2 years with AML may have characteristics similar to that of infants. Thus, we analysed 723 paediatric AML patients treated on the Japanese AML99 and AML-05 trials to identify characteristics of younger children. We identified patients aged <3 years (the younger group) as a distinct subgroup. KMT2A-rearrangement (KMT2A-R), CBFA2T3-GLIS2, CBFB-MYH11 and NUP98-KDM5A were frequently found in the younger group. Prognostic analyses revealed poor 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) in patients with CBFA2T3-GLIS2 (42%, 17% and 83%, respectively) and those with NUP98-KDM5A (33%, 17% and 83%, respectively). Additionally, we identified KMT2A-R and CBFB-MYH11 as age-specific prognostic markers. Regarding KMT2A-R, the younger group had significantly better OS, EFS and CIR than the older group (aged 3 to <18 years) (P = 0·023, 0·011 and <0·001, respectively). Conversely, concerning CBFB-MYH11, the younger group had significantly poor EFS and CIR than the older group (each P < 0·001), suggesting that certain molecular markers are linked to different prognoses according to age. Therefore, we characterized patients <3 years as a distinct subgroup of paediatric AML.
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