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

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 (≤24 months 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.

Clinical Features and Long-term Outcomes of Infant Leukemias: A Review of Ten-Years' Experiences / 대한소아혈액종양학회지

PURPOSE: Infant leukemia is rare and accounts for 5% of leukemia in children. It differs from childhood leukemia in biologic and clinical features and has a poor prognosis. Research on infant leukemia is difficult due to the scarcity of cases. We studied the clinical progress and prognosis of infant leukemia diagnosed in our hospital, in order to contribute to the treatment and prognosis of infant leukemia. METHODS: The patients who were diagnosed with leukemia in the first 12 months of life were analysed between January 1991 and December 2000 in Yonsei Medical Center. We analysed the sex, age, clinical features, treatment outcome, prognostic factor, and survival rate. RESULTS: Among a total of 41 cases, 19 cases were diagnosed with acute lymphoblastic leukemia (ALL), 15 cases with acute myelogenous leukemia (AML), 2 cases with chronic myelogenous leukemia (CML), and 5 cases were unclassifed. Twenty-two were males and 19 females; age at diagnosis was 4 months in ALL, 8 months in AML, and 4 months in CML. Common clinical features at diagnosis were pale appearance and fever, others were poor oral intake, abdominal distension, and irritability. Hyperleukocytosis with average over 20,000/mm3, anemia, and thrombocytopenia were seen. By immunologic surface marker analysis, 8 of 15 B-lineage ALL were CALLA negative, early pre-B ALL. The remission induction rate was 79% in ALL and 60% in AML. The 5 year-survival rate of 41 patients was 29.2%. Sex, age at diagnosis, white blood cell count > 50 109/L, hepatomegaly, and CNS involvement were not prognostic factors. CONCLUSION: Infant leukemia differs from childhood leukemia in biological and clinical features and has a poor prognosis. Therefore, further clinical research is needed to improve the outcome of infant leukemia.