Figure 1.
![Incidence statistics of childhood acute leukemias in 2020 in WHO regions. a. Number of new cases; b. Number of new deaths [1,10]](https://sciendo-parsed.s3.eu-central-1.amazonaws.com/65e6324ea96a436ce011782e/j_ahem-2023-0023_fig_001.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Content-Sha256=UNSIGNED-PAYLOAD&X-Amz-Credential=ASIA6AP2G7AKDKDSK32F%2F20260305%2Feu-central-1%2Fs3%2Faws4_request&X-Amz-Date=20260305T170659Z&X-Amz-Expires=3600&X-Amz-Security-Token=IQoJb3JpZ2luX2VjEAgaDGV1LWNlbnRyYWwtMSJHMEUCIHZNSHV9qAn9G%2FYdEeJzoqWDC%2BhxfvvjikV%2FiftG%2B7cIAiEA9nIRXSbm3%2Ffz0F0s52IkQmcdCrKveqt2hoPZ3GYSCLUqxgUI0f%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARACGgw5NjMxMzQyODk5NDAiDHuiXmauKnNDATpnUyqaBXY4VMnAFI4WxpQ031%2FKf6xUqPd4t3OVQPTu4QCrLUUWsxKm%2BBtwr23mWf78kkIawLxP0foRJuaWKCJIcgYGGcWx6GNc30wOFycuXr35zTECwU%2FSXxUnON3EXnuTPR%2Ben7QqW94wP2YwXSb1F99N%2Bb9GYUhE8AB6bzZfjeGsqYUKIdB4VYcaeMbEcJSFS7X1IU3cTLktkuiWcj2Vh%2BfzdE%2BJxpTS0EssORNf5Pe%2FBjt2%2FEURqqdEeBx7xrE19etH%2BcYKJcK1Lvv47zpsusSTQW8wLWH2OeMDvrn%2FR6QLAHywnOthnZvcQh8QpQeI1YbZDB0dyEAkvBDbEz5J3uPP%2F0elei8ln5VHgS%2BzGl3QZV7d9VP%2BiWEO2vVluB6kFAP6jhSLcNh3NpngByusvjOGurMf7HGlm3QNCS9G5caG1dv1ZWoKWYIAi%2BXjj1Nw1loK78Vq8XNweAKnY0YRr%2F2XSuBytJsJXZv1VplWhFFaEvJCBlhsLyB6jiVKMf9jdq%2BkFj%2FNddJWE8MlKPBhd5Z9X9%2BN%2FFVUZNIRlqJvL5CR8Ydp4h3ew21NtbGb9Bpo9kLOm1AlmpxisFJmSr6189V%2Ftv2xfvSuU%2FvqJLVcgsJVNEljZULestsMXLafFGec8DhQ22%2BbqsIhjm3uarBfWOWG4ptYoCiHiWkdVegj9TxYdG3U8T7Kw9tJlggt717A9gn%2BHHM6VXKthht6CN2ULazdLLgDGfPUp%2BBX96SVjRMCTJd8rDpbAE5Chw8JZ8qyyPGVRjQzIjh9OI%2FY2nQ0%2F%2B8yKOKJO6QNKuamjJgoplwkUmWqfyI%2FnzgnFo6jNRx1YP5FH7npxwSj040k4yX9i6vzCTE7fbuJ7SXZLrBdrzmIbXCAbsNhKbSMSZySwjD8y6bNBjqxAfE8I%2BqXkOwbhxdftbkNjmM1Tk5trpu5EL%2BYDc8GS%2B1QJOlrbfdhh%2BK8wwzTUG4l9GCkoF9sUbIrnaBYYfqwJu7z4KKfmG%2FN8%2BUjF0w19AMco079L8%2BW3QengL8E4gBK9rE%2FfcTwWzOodVu799yYHHFreo0DgJrxGNmV0zZMtXOmNTH4gQA6UjijmDgq3sH0OzctFGkfhQ6WqmCpdqaurL1bjVFRo77yyqu3j5DV85tR1w%3D%3D&X-Amz-Signature=b3fe60653f7c54d970f42e1b9f17ba316eb892eaa02ac5f809d1f7c738dcef77&X-Amz-SignedHeaders=host&x-amz-checksum-mode=ENABLED&x-id=GetObject)
Figure 2.
![Incidence trends of pediatric leukenia in 2020–2030. a. Percent of new cases; b. Percent of new deaths [16]](https://sciendo-parsed.s3.eu-central-1.amazonaws.com/65e6324ea96a436ce011782e/j_ahem-2023-0023_fig_002.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Content-Sha256=UNSIGNED-PAYLOAD&X-Amz-Credential=ASIA6AP2G7AKDKDSK32F%2F20260305%2Feu-central-1%2Fs3%2Faws4_request&X-Amz-Date=20260305T170659Z&X-Amz-Expires=3600&X-Amz-Security-Token=IQoJb3JpZ2luX2VjEAgaDGV1LWNlbnRyYWwtMSJHMEUCIHZNSHV9qAn9G%2FYdEeJzoqWDC%2BhxfvvjikV%2FiftG%2B7cIAiEA9nIRXSbm3%2Ffz0F0s52IkQmcdCrKveqt2hoPZ3GYSCLUqxgUI0f%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARACGgw5NjMxMzQyODk5NDAiDHuiXmauKnNDATpnUyqaBXY4VMnAFI4WxpQ031%2FKf6xUqPd4t3OVQPTu4QCrLUUWsxKm%2BBtwr23mWf78kkIawLxP0foRJuaWKCJIcgYGGcWx6GNc30wOFycuXr35zTECwU%2FSXxUnON3EXnuTPR%2Ben7QqW94wP2YwXSb1F99N%2Bb9GYUhE8AB6bzZfjeGsqYUKIdB4VYcaeMbEcJSFS7X1IU3cTLktkuiWcj2Vh%2BfzdE%2BJxpTS0EssORNf5Pe%2FBjt2%2FEURqqdEeBx7xrE19etH%2BcYKJcK1Lvv47zpsusSTQW8wLWH2OeMDvrn%2FR6QLAHywnOthnZvcQh8QpQeI1YbZDB0dyEAkvBDbEz5J3uPP%2F0elei8ln5VHgS%2BzGl3QZV7d9VP%2BiWEO2vVluB6kFAP6jhSLcNh3NpngByusvjOGurMf7HGlm3QNCS9G5caG1dv1ZWoKWYIAi%2BXjj1Nw1loK78Vq8XNweAKnY0YRr%2F2XSuBytJsJXZv1VplWhFFaEvJCBlhsLyB6jiVKMf9jdq%2BkFj%2FNddJWE8MlKPBhd5Z9X9%2BN%2FFVUZNIRlqJvL5CR8Ydp4h3ew21NtbGb9Bpo9kLOm1AlmpxisFJmSr6189V%2Ftv2xfvSuU%2FvqJLVcgsJVNEljZULestsMXLafFGec8DhQ22%2BbqsIhjm3uarBfWOWG4ptYoCiHiWkdVegj9TxYdG3U8T7Kw9tJlggt717A9gn%2BHHM6VXKthht6CN2ULazdLLgDGfPUp%2BBX96SVjRMCTJd8rDpbAE5Chw8JZ8qyyPGVRjQzIjh9OI%2FY2nQ0%2F%2B8yKOKJO6QNKuamjJgoplwkUmWqfyI%2FnzgnFo6jNRx1YP5FH7npxwSj040k4yX9i6vzCTE7fbuJ7SXZLrBdrzmIbXCAbsNhKbSMSZySwjD8y6bNBjqxAfE8I%2BqXkOwbhxdftbkNjmM1Tk5trpu5EL%2BYDc8GS%2B1QJOlrbfdhh%2BK8wwzTUG4l9GCkoF9sUbIrnaBYYfqwJu7z4KKfmG%2FN8%2BUjF0w19AMco079L8%2BW3QengL8E4gBK9rE%2FfcTwWzOodVu799yYHHFreo0DgJrxGNmV0zZMtXOmNTH4gQA6UjijmDgq3sH0OzctFGkfhQ6WqmCpdqaurL1bjVFRo77yyqu3j5DV85tR1w%3D%3D&X-Amz-Signature=8897e39854b4db5d93a3b420faf5f137d6efe768fe9c7b903453cc0e40b45474&X-Amz-SignedHeaders=host&x-amz-checksum-mode=ENABLED&x-id=GetObject)
Figure 3.
![a. Incidence percantage of childhood ALL by age; b. Incidence percantageof childood AML by age [17,18,19]](https://sciendo-parsed.s3.eu-central-1.amazonaws.com/65e6324ea96a436ce011782e/j_ahem-2023-0023_fig_003.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Content-Sha256=UNSIGNED-PAYLOAD&X-Amz-Credential=ASIA6AP2G7AKDKDSK32F%2F20260305%2Feu-central-1%2Fs3%2Faws4_request&X-Amz-Date=20260305T170659Z&X-Amz-Expires=3600&X-Amz-Security-Token=IQoJb3JpZ2luX2VjEAgaDGV1LWNlbnRyYWwtMSJHMEUCIHZNSHV9qAn9G%2FYdEeJzoqWDC%2BhxfvvjikV%2FiftG%2B7cIAiEA9nIRXSbm3%2Ffz0F0s52IkQmcdCrKveqt2hoPZ3GYSCLUqxgUI0f%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARACGgw5NjMxMzQyODk5NDAiDHuiXmauKnNDATpnUyqaBXY4VMnAFI4WxpQ031%2FKf6xUqPd4t3OVQPTu4QCrLUUWsxKm%2BBtwr23mWf78kkIawLxP0foRJuaWKCJIcgYGGcWx6GNc30wOFycuXr35zTECwU%2FSXxUnON3EXnuTPR%2Ben7QqW94wP2YwXSb1F99N%2Bb9GYUhE8AB6bzZfjeGsqYUKIdB4VYcaeMbEcJSFS7X1IU3cTLktkuiWcj2Vh%2BfzdE%2BJxpTS0EssORNf5Pe%2FBjt2%2FEURqqdEeBx7xrE19etH%2BcYKJcK1Lvv47zpsusSTQW8wLWH2OeMDvrn%2FR6QLAHywnOthnZvcQh8QpQeI1YbZDB0dyEAkvBDbEz5J3uPP%2F0elei8ln5VHgS%2BzGl3QZV7d9VP%2BiWEO2vVluB6kFAP6jhSLcNh3NpngByusvjOGurMf7HGlm3QNCS9G5caG1dv1ZWoKWYIAi%2BXjj1Nw1loK78Vq8XNweAKnY0YRr%2F2XSuBytJsJXZv1VplWhFFaEvJCBlhsLyB6jiVKMf9jdq%2BkFj%2FNddJWE8MlKPBhd5Z9X9%2BN%2FFVUZNIRlqJvL5CR8Ydp4h3ew21NtbGb9Bpo9kLOm1AlmpxisFJmSr6189V%2Ftv2xfvSuU%2FvqJLVcgsJVNEljZULestsMXLafFGec8DhQ22%2BbqsIhjm3uarBfWOWG4ptYoCiHiWkdVegj9TxYdG3U8T7Kw9tJlggt717A9gn%2BHHM6VXKthht6CN2ULazdLLgDGfPUp%2BBX96SVjRMCTJd8rDpbAE5Chw8JZ8qyyPGVRjQzIjh9OI%2FY2nQ0%2F%2B8yKOKJO6QNKuamjJgoplwkUmWqfyI%2FnzgnFo6jNRx1YP5FH7npxwSj040k4yX9i6vzCTE7fbuJ7SXZLrBdrzmIbXCAbsNhKbSMSZySwjD8y6bNBjqxAfE8I%2BqXkOwbhxdftbkNjmM1Tk5trpu5EL%2BYDc8GS%2B1QJOlrbfdhh%2BK8wwzTUG4l9GCkoF9sUbIrnaBYYfqwJu7z4KKfmG%2FN8%2BUjF0w19AMco079L8%2BW3QengL8E4gBK9rE%2FfcTwWzOodVu799yYHHFreo0DgJrxGNmV0zZMtXOmNTH4gQA6UjijmDgq3sH0OzctFGkfhQ6WqmCpdqaurL1bjVFRo77yyqu3j5DV85tR1w%3D%3D&X-Amz-Signature=628a38b9afe1789d8379b30944e74a9a9e27bce6602deafbb800dd50d8d928ec&X-Amz-SignedHeaders=host&x-amz-checksum-mode=ENABLED&x-id=GetObject)
Estimated number of new cases and mortality in 2020 for childhood leukemia [20,21]
| Population | New incident | Mortality | ||
|---|---|---|---|---|
| Females | Male | Females | Male | |
| WHO South-East Asia | 40.8 % | 59.2 % | 38.3 % | 61.7 % |
| WHO Western Pacific | 40.6 % | 59.4 % | 43.1 % | 56.9 % |
| WHO Americas | 44 % | 56 % | 41.5 % | 58.5 % |
| WHO East Mediterranean | 43.5 % | 56.5 % | 40.1 % | 59.9 % |
| WHO Europe | 41.7 % | 58.3 % | 42.1 % | 57.9 % |
| WHO Africa | 42.3 % | 57.7 % | 43.9 % | 56.1 % |
| all WHO regions | 42.1 % | 57.9 % | 41.5 % | 58.5 % |
Genetic predisposition to childhood leukemia
| Acquired syndromes/Genetic disorders | Type of leukemia | Mutation | |
|---|---|---|---|
| Down Syndrome | |||
| Down Syndrome (DS) | ALL/AML |
| |
| DNA repair gene syndromes and chromosomal instability syndromes | |||
| Fanconi anemia (FA) | MDS/AML | FANCA | |
| Bloom’s syndrome (BS) |
| BLM | |
| Ataxia-telangiectasia (AT) | ALL | ATM | |
| Constitutional Mismatch Repair Deficiency (CMMRD) | ALL |
| |
| Robertson translocation(RT) | ALL | ||
| Tumor suppressor gene syndromes | |||
| Li-Fraumeni syndrome(LFS) | ALL | TP53 | |
| Neurofibromatosis (NF1) | ALL AML (JMML) | NF1 | |
| Beckwith-Wiedemann syndrome (BWS) | ALL | CDKN1C | |
| Pure familial leukemia | |||
| Acquired monosomy 7 | MDS/AML | Unknown | |
| Hereditary platelet disorders (HPDs) | MDS/AML |
| |
| Bone marrow failure syndromes | |||
| Shwachman-Diamond syndrome (SDS) | AML | SDS | |
| Diamond Blackfan anemia (DBA) | MDS/AML | DBA | |
| Congenital amegakaryocytic thrombocytopenia (CAMT) | MDS/AML | c-Mpl | |
| Cyclic neutropenia (CyN) | MDS/AML | ELANE | |
| Severe congenital neutropenia (SCN) | AML | ELANE HAX1 | |
| Amegakaryocytic thrombocytopenia (AMT) | MDS/AML | c-MPL | |
| Hereditary platelet disorders (HPDs) | MDS/AML |
| |
| Aplastic anemia (AA) | MDS/AML |
| |
The International Consensus Classification of AML [9]
| AML with defining genetic abnormalities |
| AML with RUNX1::RUNX1T1 Fusion |
| AML with CBFB::MYH11 Fusion |
| Acute promyelocytic leukaemia with PML::RARA Fusion |
| AML with KMT2A rearrangement |
| AML with DEK::NUP214 Fusion |
| AML with MECOM rearrangement |
| AML with RBM15::MRTFA Fusion |
| AML with NUP98 rearrangement |
| AML with other (rare) defined genetic alterations |
| AML with NPM1 mutation |
| AML with CEBPA mutation |
| AML defined by differentiation |
| AML with minimal differentiation |
| AML without maturation |
| AML with maturation |
| Acute myelomonocytic leukemia |
| Acute monoblastic/monocytic leukemia |
| Pure erythroid leukemia |
| Acute megakaryoblastic leukemia |
| Acute basophilic leukemia |
The International Consensus Classification of ALL [6]
| B-ALL with t(12;21)(p13.2;q22.1)/ETV6::RUNX1 |
| B-ALL. hyperdiploid |
| B-ALL. low hypodiploid |
| B-ALL. near haploid |
| B-ALL with t(5;14)(q31.1;q32.3)/IL3::IGH |
| B-ALL with t(1;19)(q23.3;p13.3)/TCF3::PBX1 |
| B-ALL. BCR::ABL1–like, ABL-1 class rearranged |
| B-ALL. BCR::ABL1–like, JAK-STAT activated |
| B-ALL. BCR::ABL1–like, NOS (undefined) |
| B-ALL with iAMP21 |
| B-ALL with MYC rearrangement |
| B-ALL with DUX4 rearrangement |
| B-ALL with MEF2D rearrangement |
| B-ALL with ZNF384(362) rearrangement |
| B-ALL with NUTM1 rearrangement |
| B-ALL with HLF rearrangement |
| B-ALL with UBTF::ATXN7L3/PAN3,CDX2 (“CDX2/UBTF”) |
| B-ALL with mutated IKZF1 N159Y |
| B-ALLwith mutated PAX5 P80R |
| Provisional entity: B-ALL. ETV6::RUNX1-like |
| Provisional entity: B-ALL. with PAX5 alteration |
| Provisional entity: B-ALL. with mutated ZEB2 (p.H1038R)/IGH::CEBPE |
| Provisional entity: B-ALL. ZNF384 rearranged-like |
| Provisional entity: B-ALL. KMT2A rearranged-like |
| B-ALL, NOS (undefined) |
| T-ALL |
| Early T-cell precursor ALLwith BCL11B rearrangement |
| Early T-cell precursor ALL. NOS |
| T-ALL. NOS |
| Provisional entity: natural killer cell ALL |