Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards
Lika'a Fasih Y Al-Kzayer1, Le Thanh N Uyen, Mazin Faisal Al-Jadiry
1Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Nagano, Japan.
Insights
This study analyzed genetic mutations in 134 Iraqi children with acute myelogenous leukemia (AML). Molecular diagnostics revealed common subtypes and identified prognostic genetic abnormalities, guiding treatment strategies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Limited molecular diagnostic capabilities for cancer in Iraq.
- Pediatric acute myelogenous leukemia (AML) requires precise genetic profiling for effective treatment.
Purpose of the Study:
- To perform a genetic analysis of pediatric AML in Iraq, identifying Class I and II aberrations.
- To assess the feasibility of using Flinders Technology Associates (FTA) filter paper cards for molecular diagnostics in resource-limited settings.
Main Methods:
- Collected peripheral blood or bone marrow samples from 134 Iraqi children with AML (≤15 years).
- Utilized DNA sequencing, nested RT-PCR, long-distance inverse-PCR, and GeneScan for mutation analysis.
- Employed FTA filter paper cards for sample preservation and transport.
Main Results:
- FAB subtypes M2 (33.6%) and M3 (17.9%) were most prevalent.
- Identified mutations including FLT3-ITD (14.9%), PML-RARA (17.9%), RUNX1-RUNX1T1 (14.2%), and MLL rearrangements (18.7%).
- Approximately 30% carried favorable genetic abnormalities; 10% had high FLT3-ITD burden requiring specialized treatment.
Conclusions:
- Molecular diagnostics, even with FTA cards, can guide treatment for pediatric AML in underdeveloped countries.
- Acute promyelocytic leukemia (APL) is notably frequent in Iraqi pediatric AML cases.
- Genetic profiling is crucial for identifying patients needing intensive therapies like allogeneic hematopoietic stem cell transplantation.
Abstract:
The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.
