t(3;21)(q26;q22) with AML1 rearrangement in a de novo childhood acute monoblastic leukaemia

Abstract

t(3;21)(q26;q22) is a recurrent chromosomal abnormality in Philadelphia-positive chronic myeloid leukaemia in blast crisis and in treatment-related myelodysplastic syndrome and acute myeloid leukaemia. The molecular consequences of the t(3;21) are presently being unravelled; various transcripts between the AML1 gene in 21q22 and several unrelated genes, i.e. EAP, EVI1 and MDS1, in 3q26 are generated, resulting in the formation of a chimaeric transcription factor. The t(3;21) has only rarely been described in de novo leukaemias and never before in an acute leukaemia in a child. We here present the clinical, cytogenetic and molecular genetic findings in a boy with a de novo acute monoblastic leukaemia with t(3;21)(q26;q22) and AML1 rearrangement.

Human AML1/MDS1/EVI1 fusion protein induces an acute myelogenous leukemia (AML) in mice: A model for human AML

“…However, both AML-M4 and M5 subtypes have been found in cases of t(3;21)-associated AML (1,29). In this study, expression of GFP helped us demonstrate that both myelocytic and monocytic leukemic cells exist in AME mice ( Fig.…”

“…Studying the role of these fusion transcription factors in leukemogenesis is important for understanding the molecular mechanism of leukemias. A reciprocal translocation between chromosomes 3, band q26, and 21, band q22, has been found in certain patients with chronic myelogenous leukemia during blast phase (CML-BC), in patients with therapy-related myelodysplasia͞acute myelogenous leukemia (t-MDS͞t-AML), and on rare occasions in de novo acute myelogenous leukemia (AML) (1,2). The t(3;21) translocation can result in fusion of the AML1 gene on chromosome 21 to several genes on chromosome 3, namely EAP, MDS1, and MDS1͞EVI1 (reviewed in refs.…”

The EVI1 gene in myeloid leukemia

“…44,64 Because the t(3;21) appears in CML only during the blast crisis of the disease, it is possible that activation of the gene may play a role in the progression of the disease from chronic to acute phase. However, recently a t(3;21) was detected in a patient with de novo childhood AML, 65 indicating therefore that this translocation is not restricted to adult patients with secondary leukemias or with CML during the acute phase. Activation of EVI1 was also reported in CML-BC patients with apparently normal chromosomes 3, [66][67][68] and results from several groups would indicate that a correlation exists between the activation of EVI1 (either as a fusion protein or by overexpression), and the progression of CML from the chronic to the acute phase.…”

Transcription factors and translocations in lymphoid and myeloid leukemia

“…220,221 This translocation, as in the fusion protein AML1/ETO, involves the transcription factor AML1, described above.…”