Down syndrome associated childhood myeloid leukemia with yet unreported acquired chromosomal abnormalities and a new potential adverse marker: dup(1)(q25q44)

Abstract

BackgroundChildren with constitutional trisomy 21, i.e. Down syndrome (DS, OMIM #190685) have a 10 to 20-fold increased risk for a hematopoietic malignancy. They may suffer from acute lymphoblastic leukemia or acute myeloid leukemia (AML). AML referred to as myeloid leukemia of Down syndrome (ML-DS) is observed especially after birth at an early gestational age and characterized by enhanced white blood cell count, failure of spontaneous remission, liver fibrosis or liver dysfunction, and is significantly associated with early death. There are only few studies yet focusing on the clonal cytogenetic changes during evolution of ML-DS.Case presentationIn a 1.4-year-old boy with DS an immunophenotype consistent with AML-M1 according to French-American-British (FAB) classification was diagnoses. Cytogenetic and molecular cytogenetic analyses revealed, besides constitutional free trisomy 21, an unbalanced translocation as der(16)t(1;16)(q25.3;q24), plus a balanced translocation t(3;20)(q25;q13.1). A poor clinical outcome was observed here.ConclusionsTo the best of our knowledge, an ML-DS case associated with identical acquired chromosomal abnormalities was not previously reported. Our findings suggest that especially partial trisomy 1q25 to 1q44 may be indicative for a poor prognosis in ML-DS.

Acute megakaryoblastic leukaemia shows high frequency of chromosome 1q aberrations and dismal outcome

“…Furthermore, gains of 1q are described in 4%–16% of paediatric ML‐DS patients 27,28 . There are further case reports on 1q aberrations in ML‐DS, that identified 1q31–1q44 as the recurrent amplified region 29–31 . The overlapping region from our cohort and data from ML‐DS analyses is 1q31–1q32 and includes the genes PTPRC , ELK4 , MDM4 and SLC45A3 with documented roles in cancer development 32,33 .…”

“…27,28 There are further case reports on 1q aberrations in ML-DS, that identified 1q31-1q44 as the recurrent amplified region. [29][30][31] The overlapping region from our cohort and data from ML-DS analyses is 1q31-1q32 and includes the genes PTPRC, ELK4, MDM4 and SLC45A3 with documented roles in cancer development. 32,33 However, further analyses are needed to identify a possible mechanism of action and prognostic relevance in AMKL.…”

Down syndrome presenting with different hematological manifestations: A case series of four cases

“…Although AML-M7 is considered to be the most common morphological subtype seen in patients with DS, other AML FAB subtypes have also been considered in ML-DS including M0, M1/M2, and M6, less frequently. [ 8 ] In our study case 4 has been diagnosed as AML-M2.…”

HeliDye1: helquat fluorogenic probe specific for AT-rich DNA duplexes

“…leukaemias, Down syndrome). 46,47 Due to an exceptional AT-specificity of HeliDye1, we achieved higher contrast of banding in comparison with Wright's staining (for comparison of all chromosomes and full karyotypes see Fig. S17, S18 and S19 SI).…”

“…A chromosomal banding is usually based on AT or GC base pair specificity and is used for assignment of chromosomes and diagnostic purposes (e.g. leukaemias, Down syndrome) 45,46 . Due to superior AT-specificity of HeliDye1 over other dyes, we anticipate that HeliDye1 could provide the banding observable directly in the mitotic cell without necessity of chromosome isolation.…”