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Cytogenetic findings in acute leukaemias of infants
F Lampert1, J Harbott, J Ritterbach
1Kinderpoliklinik, Justus-Liebig-Universität, Giessen, Germany.
Insights
Infant leukemia, including acute lymphoblastic leukemia (ALL) and acute myelocytic leukemia (AML), shows unique genetic features like 11q23 aberrations, differing from older children. These early hematopoietic stem cell cancers present distinct clinical and cellular characteristics.
Area of Science:
- Pediatric Oncology
- Hematology
- Cancer Genetics
Background:
- Leukemia in infants is rare but presents distinct biological features compared to older children.
- Understanding infant leukemia's unique characteristics is crucial for diagnosis and treatment.
- Karyotypic analysis provides insights into the genetic underpinnings of infant leukemias.
Purpose of the Study:
- To characterize the distinct cytogenetic and immunophenotypic features of infant acute lymphoblastic leukemia (ALL) and acute myelocytic leukemia (AML).
- To investigate the prevalence and significance of specific chromosomal aberrations, particularly 11q23, in infant leukemias.
- To compare the leukaemogenesis in infants with that in older children.
Main Methods:
- Karyotypic analysis of leukemia cells from 48 infants (28 ALL, 20 AML) under one year of age.
- Immunophenotypic analysis to determine cell lineage and differentiation status.
- Comparison of genetic and cellular features with those of older pediatric leukemia patients.
Main Results:
- Infant ALL lacked hyperdiploidy and showed increased pseudodiploidy, with 46% having 11q23 aberrations (e.g., t(4;11)).
- Infant AML also frequently featured 11q23 abnormalities (45%, e.g., t(9;11)), totaling nearly 50% of infant leukemia karyotypes.
- Infant ALL predominantly showed CALLA-negative, pre-pre-B immunophenotype; infant AML was often monocytic subtype, with some cases exhibiting biphenotypic morphology.
Conclusions:
- Leukemogenesis in infants is a rare event originating from very early hematopoietic stem cells, likely due to frequent gene rearrangement errors at FRA11B.
- Infant leukemia exhibits unique clinical and cellular features, distinguishing it from leukemia in older age groups.
- The high incidence of 11q23 aberrations underscores its critical role in infant leukemia development.
Abstract:
Of 706 children, 528 with acute lymphoblastic leukaemia (ALL) and 178 with acute myelocytic leukaemia (AML), whose leukaemia karyotypes could be successfully analysed, 48 were infants less than 1 year of age, 28 with ALL (5% of ALL patients) and 20 with AML (11% of AML patients). In contrast to older children. ALL-leukaemocytogenetics in infants was characterised by lack of hyperdiploidy with over 50 chromosomes and higher incidence of pseudodiploidy. Thirteen (= 46%) infants had an 11q23 aberration, and 11 of them had t(4;11). In AML, nine (= 45%) infants also had an 11q23 abnormality, e.g. t(9;11). Thus, the 11q23 aberration was present in almost 50% of all leukaemia karyotypes of infants. In ALL of infants, the CALLA negative, pre-pre-B immunophenotype prevailed. In AML of infants, the monocytic subtype dominated. A biphenotypic morphology (lymphoid-monocytic) with the expression of lymphoid and myeloid antigens was seen in several ALL and AML cases. In conclusion, leukaemogenesis in infants is a rare event, arising in stem cells of very early hematopoietic differentiation (probably due to gene rearrangement errors, most frequently at FRA11B), and differs from leukaemogenesis in older age groups by unique clinical and cellular features.