Pediatric Acute Megakaryoblastic Leukemia with T(4;11) (Q21;Q23)/MLL-AF4 Fusion Transcript: A Case Report

Case Report

Ann Nurs Res Pract. 2022; 7(1): 1050.

Pediatric Acute Megakaryoblastic Leukemia with T(4;11) (Q21;Q23)/MLL-AF4 Fusion Transcript: A Case Report

Li Zhang1#, Hanyi Hou2#, Xiurong Gao1, Muxia Yan1, Yanmei Li1 and Yiqian Wang2*

1Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China

2Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China

#These authors have contributed to this work

*Corresponding author: Yiqian Wang, Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, China

Received: July 26, 2022; Accepted: August 17, 2022; Published: August 24, 2022


Acute Megakaryoblastic Leukemia (AMKL) is a rare and biologically heterogenous subtype of Acute Myeloid Leukemia (AML) with a diverse cytogenetic profile. Mix-lineage leukemia (MLL) rearrangements are commonly found in infant Acute Lymphoblastic Leukemia (ALL) and childhood AML. However, the occurrence of MLL rearrangements in AMKL is very rare. Here, we report a pediatric case of AMKL with MLL- AF4 fusion derived from t(4;11) (q21;q23). To our knowledge, the case has not been reported from China. Our observation supports understanding of molecular diversity in AMKL. The varying molecular features of AMKL are warranted to fully understand to develop novel therapeutic strategies.

Keywords: Acute megakaryoblastic leukemia; MLL-AF4 fusion gene; t(4;11)(q21;q23)


Acute Leukemia (AL) is characterized by the clonal expansion of Hematopoietic Stem Cells (HSCs) or progenitors, blocking their differentiation into multiple blood lineages [1,2]. AL is divided into Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), mainly based on the type of leukemic-initiating cell lineage [3]. In the past few decades, the French-American-British (FAB) Cooperative Group has classified AML on the basis of morphologic features and number of blast cells. Acute Megakaryoblastic Leukemia (AMKL), resulting from the malignant accumulation of progenitors in the megakaryocyte lineage, occurs predominantly in children and is recognized as AML-M7 according to FAB system [4,5]. AMKL is divided into two major subgroups: patients with Down syndrome (DS-AMKL) and patients without Down syndrome (non-DS-AMKL) with the outcome of the latter one is generally poor with worse prognosis [6,7].

Chromosomal rearrangement of 11q23 involving the mixedlineage leukemia (MLL) gene is commonly found in childhood ALL and AML [8]. The most common rearrangement disrupting MLL gene involves a reciprocal translocation between MLL and a partner gene, resulting in a chimeric protein composed of the N-terminus domain of MLL and C-terminus domain of the partner gene. AF4 at 4q21 is a common partner for MLL, and MLL- AF4 fusion gene is observed in about 10% of patients diagnosed with B-cell ALL [9]. Involvement of the MLL-AF4 fusion transcript in AML is rarely found. Here, we present the first case of a Chinese pediatric AMKL patient with MLLAF4 fusion gene at our institution.

Case Report

A 5-year-old boy presented with fever and hemorrhage was admitted to our hospital. Physical examination detected anemia and petechiae on the neck and chest, as well as hepatosplenomegaly. In addition, cervical, axillary, and inguinal lymph nodes were negligible. A complete blood count and peripheral smear showed a White Blood Cell (WBC) count of 6.7×109/L, with 9% mature granulocytes, 82% lymphocytes, 1% monocytes and 8% blasts. The hemoglobin concentration was 85g/L, and the platelet count was 45×109/L. The bone marrow aspiration showed myeloid hyperplasia with 2% myeloid cells, 1% erythroid cells, 6% lymphoid cells and 91% blasts. Moreover, the blast cells had pale blue-gray cytoplasm, round nuclei with reticulated chromatin, high Nucleus-to-Cytoplasm (N/C) ratio and pseudopod formation (Figure 1A). Auer rods were not present, and some blasts showed cytoplasmic blebs. Platelet shedding was observed. Cytochemical staining showed that the blasts negative peroxidase (POX) -staining, positive Periodic Acid-Schiff (PAS) staining, and demonstrated alpha-naphthyl acetate esterase (alpha- NAE) reactivity (Figure 1B-C). Flow cytometry showed that the blast cells were positive for CD7, CD9, CD13, CD33, CD34, CD36, CD41a, CD42b and CD61 (Figure 2). Based on the above clinical observations, a diagnosis of AMKL (AML-M7) was made. Furthermore, Chromosomal analysis of the Bone Marrow (BM) leukemic blasts was performed at initial diagnosis using standard G-banding methods. The cytogenetic result revealed an abnormal karyotype with 46, XY, t(4;11) (q21;q23), del(12)(p11)[9]/46, XY[1], which indicated that the patient did not have DS although with a typical t(4;11) translocation. Fluorescence in situ hybridization (FISH) analysis using the MLL dual color ‘break- apart’ probe confirmed the rearrangement of MLL gene (Figure 3A). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to identify the partner gene fused to MLL. PCR primers and PCR protocols were adopted from Pallisgaard et al [10]. Appropriate positive and negative controls were also included. The PCR analysis confirmed the existence of the MLL-AF4 transcript (Figure 3B). The patient received chemotherapy according to Chinese Childhood AML Cooperative Study Group Protocol including daunomycin and cytarabine, and achieved a Complete Remission (CR). Thereafter, the patient received one course of consolidation chemotherapy (daunomycin, cytarabine and etoposide) and one course of intensification chemotherapy with high-dose cytarabine. Later, the patient was discharged from the hospital for personal reason.