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

Abstract

BackgroundAcute 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 (≤24 months old), based on the presence of hemophagocytosis by blast cells at diagnosis.MethodsA 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.ResultsEleven 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.ConclusionsOur 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.

Uncommon cytogenetic abnormalities identifying high-risk acute myeloid leukemia in children

“…Morphologically, most t(8;16)-positive patients are classified in M4 and M5 FAB groups and show erythrophagocytosis [26,27,57], as reported in adults (Table 1). The majority of t(8;16)(p11;p13) patients are positive for the myeloid markers MPO, CD13, CD33 and/or CD14 (the latter indicates monocytic differentiation); few cases show positivity for the stem cell markers CD117 and CD34; almost all cases are positive for CD15 and HLA-DR [26,27,[58][59][60]. Erythrophagocytosis and leukemia cutis are both associated with CD56 expression [26,27].…”

Hemophagocytosis or emperipolesis by lymphoblast after rapid transformation of chronic myeloid leukemia

“…HLH is a rare disorder of the immune system result of a direct immune activation process familial or due to infectious diseases, autoimmune diseases, malignancies. At least five features can be seen: 1) fever; 2) splenomegaly; 3) cytopenias at least two or three lineages; 4) hypertriglyceridemia and/or hypofibrinogenemia; 5) hemophagocytosis [1][2][3][4].…”

“…It also has been described in malignant cells, including blast cells in the blast phase of CML. Leukemia blasts containing hematopoietic cells have been described in ALL with t(12;21), T-ALL and mainly in megakaryocytic with t(16;21) and t(1;22) or monoblastic with t(8;16), but not always associated with HLH [1][2][3][4][5].…”

Acute myeloid leukaemia at an early age: Reviewing the interaction

“…The recurrent KMT2A- r is highly prevalent in our series of i-AML cases. Other chromosomal translocations, such as the t(7;12)(q36;p13)/ MNX1 - ETV6 , t(8;16)(p11;p13)/ MYST3-CREBBP , t(1;22)(p13;q13)/ RBM15 - MKL1 and inv(16)(p13.3q24.3)/ CBFA2T3 - GLIS2 , are all specifically associated with i-AML in variable prevalent frequencies that encompass the remaining 30% of aberrations [ 7 – 11 ].…”