Myelodysplasia and acute megakaryoblastic leukemia in down's syndrome

Zipursky, Alvin; Thorner, Paul; Harven, Étienne de; Christensen, Hilary; Doyle, John

doi:10.1016/0145-2126(94)90111-2

Cited by 137 publications

(86 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2,4 The percentage of patients with DS among paediatric AML patients in our study has increased continuously since study AML-BFM 78: study 78 ¼ 1.9%; study 83 ¼ 5.6%; study 87 ¼ 8.1%; study 93 ¼ 9.7%; and study 98 ¼ 12.9%. These data also indicate an increase in reporting DS patients to our study centre in the last decade compared to former times.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the poor response and low survival rate (eg 14% reported by Athale et al 24 ) in non-Down children with FAB M7, a high cure rate has been reported in DS AMKL patients. 4,6,21,24 However, a significantly lower survival estimation for de novo AML M7 than for other subtypes of de novo AML was reported, 24 which could not be confirmed by the results of studies AML-BFM 93 and 98: 3-year survival in 55 non-DS children with FAB M7 was 5677%, thus similar to other non-DS high-risk patients (5772%), but significantly lower compared to DS patients with AMKL (8474%).…”

Section: Discussionmentioning

confidence: 99%

“…1 A peak incidence of acute myelogenous leukaemia (AML) in DS children under 4 years of age was found, 2,3 and in these patients, a marked increase of the megakaryoblastic subtype (FAB M7) was seen. 4 Frequently, DS patients show a myelodysplastic phase preceding the development of AML. 4,5 In the 1970s and 1980s, outcome in children with DS and AML was thought to be poor.…”

Section: Introductionmentioning

confidence: 99%

“…4 Frequently, DS patients show a myelodysplastic phase preceding the development of AML. 4,5 In the 1970s and 1980s, outcome in children with DS and AML was thought to be poor. First reports about high rates of event-free survival (EFS) with intensive AML treatment were submitted by the Paediatric Oncology Group.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity

et al. 2005

View full text Add to dashboard Cite

Despite improved prognosis in acute myelogenous leukaemia (AML) children with Down syndrome (DS), therapy-related toxicity remained a problem. We compared 67 DS patients from study AML-BFM 98 with 51 DS patients of the previous study AML-BFM 93, and the non-DS groups of both studies. Compared to non-DS patients, DS patients were treated with reduced anthracycline doses, without high-dose cytarabine/ mitoxantrone and without cranial irradiation. AML-DS patients were in median 1.8 years old, and 102/118 (86%) showed the typical morphology of acute megakaryoblastic leukaemia. In study 93, seven DS patients did not receive AML-specific chemotherapy, and treatment modifications were more common. Results improved significantly for patients treated in study 98 with a 3-year survival of 9174 vs 7077% in study 93 (P ¼ 0.001). There were no differences in outcome concerning the age groups 0-p2 and 2-p4 years (event-free survival for treated patients 0-p2 years 8374%, 2-p4 years 8177%). The cumulative incidence of relapses was significantly lower in DS (773%) than in non-DS patients (2877%). Therapy-related toxicity was generally lower in DS patients treated according to study 98. We conclude that a standardised and dose-reduced treatment schedule including the main components of AML treatment is advisable for AML children with DS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity

et al. 2005

View full text Add to dashboard Cite

show abstract

“…1 AML in DS children displays unique characteristics including a predominance of the acute megakaryocytic leukemia (AMkL) phenotype, [2][3][4][5][6][7][8][9] which is estimated to occur at a 500-fold greater frequency in DS children compared to non-DS children. 8 This suggests that trisomy 21 plays an important role in leukemogenesis. DS and non-DS children with AMkL treated with cytosine arabinoside (ara-C)/anthracycline-based protocols have extremely different treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

The role of the proto-oncogene ETS2 in acute megakaryocytic leukemia biology and therapy

LaFiura

Dombkowski

et al. 2007

Leukemia

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) in Down syndrome (DS) children has several unique features including a predominance of the acute megakaryocytic leukemia (AMkL) phenotype, higher event-free survivals compared to non-DS children using cytosine arabinoside (ara-C)/anthracycline-based protocols and a uniform presence of somatic mutations in the X-linked transcription factor gene, GATA1. Several chromosome 21-localized transcription factor oncogenes including ETS2 may contribute to the unique features of DS AMkL. ETS2 transcripts measured by real-time RT-PCR were 1.8-and 4.1-fold, respectively, higher in DS and non-DS megakaryoblasts than those in non-DS myeloblasts. In a doxycycline-inducible erythroleukemia cell line, K562pTet-on/ETS2, induction of ETS2 resulted in an erythroid to megakaryocytic phenotypic switch independent of GATA1 levels. Microarray analysis of doxycycline-induced and doxycycline-uninduced cells revealed an upregulation by ETS2 of cytokines (for example, interleukin 1 and CSF2) and transcription factors (for example, TAL1), which are key regulators of megakaryocytic differentiation. In the K562pTet-on/ ETS2 cells, ETS2 induction conferred differences in sensitivities to ara-C and daunorubicin, depending on GATA1 levels. These results suggest that ETS2 expression is linked to the biology of AMkL in both DS and non-DS children, and that ETS2 acts by regulating expression of hematopoietic lineage and transcription factor genes involved in erythropoiesis and megakaryopoiesis, and in chemotherapy sensitivities.

show abstract

Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management

Novitzky

2000

Am. J. Hematol.

View full text Add to dashboard Cite

The FAB group has defined myelodysplasia in adults but direct application of this categorization to children has been controversial. Consequently, to outline the natural history of the disease better we have retrospectively analysed case reports and series published in English between 1982 and 1996. This study also included children with juvenile chronic myelomonocytic leukaemia (JCML) and monosomy 7 (Mo7). 340 patients were described in 27 publications. The mean presentation age was 5.91 (SD 5.04) years, and 34.9% were female. Constitutional alterations were described in 68 (20%) where refractory anemia (RA) and RA with excess of blasts (RAEB) predominated and were associated with a significantly longer survival. Among all patients progression to higher forms of MDS was noted in 61 (18%). Cytogenetic anomalies were detected in 59% of 227 children, and in 67 it was to Mo7. Amid those with Mo7, the clinical and laboratory characteristics as well as survival, closely followed their FAB type. Of the treatment options described, survival was significantly higher in those who underwent bone marrow transplant (BMT) (46.9%; P = 0.00021). Among children with JMML (CMML/JCML) not receiving a BMT, time to death was shortest in those best described as JCML (absence of constitutional and karyotypic derangement, thrombocytopenia and elevated Hb F). We conclude that children with constitutional abnormalities survive longer, Mo7 disorders are clinically and morphologically heterogeneous and should not be grouped into a single entity and that CMML and JCML may have biological differences. Finally, BMT remains the treatment of choice for those with primary MDS, as intensive chemotherapy is no better than supportive measures.

show abstract

Myelodysplasia and acute megakaryoblastic leukemia in down's syndrome

Cited by 137 publications

References 21 publications

AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity

AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity

The role of the proto-oncogene ETS2 in acute megakaryocytic leukemia biology and therapy

Myelodysplastic syndromes in children. A critical review of the clinical manifestations and management

Contact Info

Product

Resources

About