CEBPA Are Independent Good Prognostic Factors in Pediatric Acute Myeloid Leukemia

Abstract To find poor prognostic factors other than karyotypes is desired to improve the treatment outcome in pediatric acute myeloid leukemia (AML). Total three hundread and eighteen patients were enrolled in Japanese Childhood AML Cooperative Treatment Protocol, AML99, from January 2000 to December 2002. We performed the mutation analysis of FLT3 and MLL in 158 patients (13 of 29 with FAB-M3, 10 of 49 with Down syndrome, 135 of 240 with other type of AML) Patients with FAB-M3 and patients with Down syndrome were treated on different protocol. Seventeen (12.6%) of 135 patients had FLT3-internal tandem duplication (ITD). The differences between AML patients with or without FLT3-ITD were significant in 4-year overall survival (OS) (35.3% vs. 86.1%, p<0.00001), disease free survival (DFS) (38.5% vs. 68.1%, p=0.0013), and relapse rate (RR) (53.8% vs. 28.5%, p=0.0029). Furthermore, MLL-partial tandem duplication (PTD) was found in 21 (15.6%) of 135 patients. The differences between patients with or without MLL-PTD were significant in 4y-OS (56.3% vs. 81.4%, p=0.013), DFS (41.7% vs. 68.3%, p=0.017), and RR (53.9% vs. 27.5%, p=0.0078). Out of 18 patients with MLL-PTD who received allo-SCT, 9 patients survived (6 of 8 in 1st CR, 3 of 4 in 2nd CR, 0 of 6 in non CR). Out of 12 patients with FLT3-ITD who received allo-SCT, 4 patients survived (4 of 6 in 1st CR, 0 of 6 in non CR). Allo-SCT is considered to be effective for the patients with TD of both genes. Coduplication of both genes was observed in 3 patients. FLT3 kinase domain mutation was found in 7.0% and MLL translocations were found in 11.4% of the patients, but both aberrations did not show poor outcome in this study. FLT3-ITD and MLL-PTD were found in 9 (25.7%) and 8 (22.9%) of 35 patients with normal karyotype. FLT3-ITD and MLL-PTD are considered to be independent poor prognostic factors of pediatric AML patients, especially in patients with normal karyotype. The different therapeutic approach including allo-SCT will be needed for these patients.

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Measurable residual disease in pediatric acute myeloid leukemia: a systematic review

Expert Review of Anticancer Therapy ◽

10.1080/14737140.2021.1860763 ◽

2021 ◽

Vol 21 (4) ◽

pp. 451-459

Author(s):

W H Segerink ◽

V de Haas ◽

G J L Kaspers

Keyword(s):

Systematic Review ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Residual Disease ◽

Pediatric Acute Myeloid Leukemia ◽

Measurable Residual Disease ◽

Acute Myeloid

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NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia

International Journal of Molecular Sciences ◽

10.3390/ijms22094575 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4575

Author(s):

Vincenza Barresi ◽

Virginia Di Bella ◽

Nellina Andriano ◽

Anna Provvidenza Privitera ◽

Paola Bonaccorso ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Mutational Analysis ◽

Integrated Analysis ◽

Induction Phase ◽

Pediatric Acute Myeloid Leukemia ◽

Expression Arrays ◽

Primary Induction ◽

Induction Failure ◽

Acute Myeloid

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for “Differentially Expressed Genes” (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.

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