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. 2016 Oct-Dec;38(4):291-297.
doi: 10.1016/j.bjhh.2016.06.005. Epub 2016 Jul 26.

Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis

Francianne Gomes Andrade  1 , Elda Pereira Noronha  1 , Rosania Maria Baseggio  2 , Teresa Cristina Cardoso Fonseca  3 , Bruno Marcelo Rocha Freire  4 , Isis M Quezado Magalhaes  5 , Ilana R Zalcberg  1 , Maria S Pombo-de-Oliveira  6
Affiliations

Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid leukemia and hemophagocytosis

Francianne Gomes Andrade et al. Rev Bras Hematol Hemoter. 2016 Oct-Dec.

Abstract

Background: Acute myeloid leukemia presenting the MYST3-CREBBP fusion gene is a rare subgroup associated with hemophagocytosis in early infancy and monocytic differentiation. The aim of this study was to define the relevant molecular cytogenetic characteristics of a unique series of early infancy acute myeloid leukemia cases (≤24months old), based on the presence of hemophagocytosis by blast cells at diagnosis.

Methods: A series of 266 infant cases of acute myeloid leukemia was the reference cohort for the present analysis. Acute myeloid leukemia cases with hemophagocytosis by blast cells were reviewed to investigate the presence of the MYST3-CREBBP fusion gene by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction.

Results: Eleven cases with hemophagocytosis were identified with hemophagocytic lymphohistiocytosis being ruled out. Six cases were classified as myelomonocytic leukemia, three as AML-M7 and two as AML-M2. In five cases, the presence of the MYST3-CREBBP fusion gene identified by molecular cytogenetics was confirmed by fluorescence in situ hybridization. All patients received treatment according to the Berlin-Frankfürt-Münster acute myeloid leukemia protocols and only one out of the five patients with the MYST3-CREBBP fusion gene is still alive.

Conclusions: Our findings demonstrate that the presence of hemophagocytosis in acute myeloid leukemia was not exclusively associated to the MYST3-CREBBP fusion gene. Improvements in molecular cytogenetics may help to elucidate more complex chromosomal rearrangements in infants with acute myeloid leukemia and hemophagocytosis.

Keywords: Acute myeloid leukemia; Hemophagocytosis; Infant leukemia; MYST3-CREBBP (or, MOZ-CBP); t(8 ;16)(p11 ;p13).

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Figures

Figure 1
Figure 1
Morphology of AML-M4 with hemophagocytosis by blast cells. Bone marrow aspiration stained by May–Grunwald–Giemsa shows myeloblast and monoblast cells with phagocytosis of red cells and lymphocytes.
Figure 2
Figure 2
FISH pattern of MYST3-CREBBP probes. Three types of hybridization patterns were observed: two red and two green signals (A); a single fusion pattern, with one red and one green signal remaining (B); and a dual fusion signal (C).
Figure 3
Figure 3
Agarose gel images of RT-PCR for MYST3-CREBBP fusion genes. Gel A, shows positive reactions for the MYST3-CREBBP fusion gene. Samples 2 (A) and 19 (B) are the positive controls in each reaction. Sample 1 (A and B) is the negative control (H2O only). Samples 3 and 5 (A) are from patients #1 and #11. In gel B, all samples are negative for the MYST3-CREBBP fusion gene; M: standard marker (100 base pairs)
See this image and copyright information in PMC

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