Rare Cytogenetic Anomalies in Two Pediatric Patients with Acute Leukemia

To the Editor,

Structural chromosomal abnormalities are frequently seen in both pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) cases [1,2,3]. Although some chromosomal abnormalities are common, other abnormalities are rarely seen [4,5]. In this study two relatively rare cytogenetic abnormalities are reported.

All procedures were performed in accordance with the Helsinki Declaration and approved by the local ethics committee (Approval No: GO 16/267-45).

Case One

CALLA+ pre-B-cell ALL was diagnosed in an 8-year-old-boy. The complete blood count (CBC) at diagnosis revealed hemoglobin of 5.5 g/dL, white blood cell (WBC) count of 2.8x109/L, and platelet count of 301x109/L. He had t(1;4)(q42;q22) in all twenty metaphases as a sole abnormality (). The ALLIC-BFM-2009 treatment protocol was started. Bone marrow examination on day 15 revealed remission. The patient was diagnosed in 2006. The last follow-up visit was in December 2019 and he is still alive.

Case Two

A girl of two and half months was diagnosed with the AML FAB-M5 phenotype. She had no comorbid disease and the diepoxybutane (DEB) test for Fanconi’s anemia was negative. CBC results at diagnosis revealed hemoglobin of 10 g/dL, WBC count of 9.2x109/L,and platelet count of 365x109/L. The AML-BFM-2004 protocol was initiated. The karyotype of the patient was 46,XX,t(1;11)(p32;q23)[19]/46,XX [1]. Bone marrow aspiration of the patient showed that she had entered the remission.

Herein, we report two rare translocations. t(1;4)(q42;q22) was found in Case 1 with ALL and this anomaly has been reported in one case to date according to the database in which we searched [6]. The previous case was also a pediatric ALL patient, as in our case [7]. While we found t(1;4)(q42;q22) as a sole abnormality in all metaphases, the anomaly was found in a complex karyotype in the previously reported case. The hybrid gene formed as a consequence of this t(1;4)(q42;q22) and its function are not known. Our case is the second reported case with this anomaly and thus contributes to the literature.

In our second case, t(1;11)(p32;q23) was found, which has been seen in a total of seven pediatric AML cases to date [6]. The ages of patients in whom this abnormality was previously detected were between 0 and 12 years, two of them being infants; our patient was 2.5 months old. When the FAB classification of the patients was examined for the previously reported cases, M0, M1, M4, and M5 were found. Hayashi et al. [8] reported this anomaly for the first time in a 7-year-old patient with AML M1 and they did not find this anomaly at diagnosis; instead, it was detected during the remission of the patient. In our case, t(1;11)(p32;q23) was present at the time of diagnosis of acute leukemia. The result of t(1;11)(p32;q23) is the MLL-EPS15 fusion gene. The role of this fusion gene in the pathogenesis of AML is not known, but it has been suggested that the coiled-coil domains of EPS15 mediate oligomerization and activate MLL [9,10,11].

The prognostic values of rare cytogenetic anomalies are unknown. The accumulation of knowledge about rare cytogenetic anomalies detected in childhood leukemia is expected to contribute to a better understanding of the pathogenesis of these diseases.