A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases

Abstract

Myelodysplastic and myeloproliferative disorders are rare in childhood and there is no widely accepted system for their diagnosis and classification. We propose minimal diagnostic criteria and a simple classification scheme which, while based on accepted morphological features and conforming with the recent suggestions of the WHO, allows for the special problems of myelodysplastic diseases in children. The classification recognizes three major diagnostic groups: (1) juvenile myelomonocytic leukemia (JMML), previously named chronic myelomonocytic leukemia (CMML) or juvenile chronic myeloid leukemia (JCML); (2) myeloid leukemia of Down syndrome, a disease with distinct clinical and biological features, encompassing both MDS and AML occurring in Down syndrome; and (3) MDS occurring both de novo and as a complication of previous therapy or pre-existing bone marrow disorder (secondary MDS). The main subtypes of MDS are refractory cytopenia (RC) and refractory anemia with excess of blasts (RAEB). It is suggested retaining the subtype of RAEB-T with 20-30% blasts in the marrow until more data are available. Cytogenetics and serial assessments of the patients are essential adjuncts to morphology both in diagnosis and classification.

Trisomy of chromosome 21 in leukemogenesis

“…The megakaryocytic leukemia of Down syndrome is a unique disease [18]. However patients with Down syndrome are also at a markedly increased risk for childhood acute lymphoblastic leukemias (ALL).…”

Gene expression signatures of pediatric myelodysplastic syndromes are associated with risk of evolution into acute myeloid leukemia

“…As relative blasts count alone is not sufficient to differentiate AML from MDS, morphological evaluation remains crucial for diagnosis of MDS. 1 Gene expression profile (GEP) analysis has proved to be a powerful tool for the identification of gene signatures associated with distinct leukemia subtypes and has helped to classify these diseases, to stratify patients into different risk classes and to identify deregulated genes involved in leukemia development. 4 --6 Only few studies on GEP of pediatric MDS have been published so far, 7 mainly due to the rarity of these disorders.…”

“…8 Here, we report results of GEP analysis on 32 BM pediatric specimens with a diagnosis of MDS according to the MDS classification proposed for pediatric patients. 1 Furthermore, specimens of 16 pediatric patients with a diagnosis of de novo AML with normal karyotype and 8 healthy BM donors, were also included in the analysis. Through GEP analysis, we aimed to characterize subgroups of MDS and to identify the genes and molecular pathways related to the progression of pediatric MDS into AML.…”

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukemia: a single center experience of 23 patients

“…1 It has also been described as juvenile chronic myeloid leukemia or chronic myelomonocytic leukemia. 2 In a recently proposed pediatric morphological classification, 3 JMML is separated from the other subtypes of MDS, that is, RA, RAEB and RAEB-t because of different characteristics. Molecular biological investigations have shown three major, mutually exclusive abnormalities in JMML patients, that is, the presence of NF1 gene mutation, 4 mutations in the Ras-signalling pathway 5 and mutations in the PTPN11 region.…”