ZNF384 rearrangement in acute lymphocytic leukemia with renal involvement as the first manifestation is associated with a poor prognosis: a case report

Abstract

Background: Novel fusion genes such as ZNF384, have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in recent years. Patients harboring ZNF384 rearrangements have a distinctive immunophenotype with weak CD10 and aberrant CD13 and/or CD33 expression. Thus, ZNF384-rearranged ALL is a unique subtype of BCP-ALL. However, research on the prognostic significance of ZNF384 rearrangements has been limited to date, especially in adolescents.

Case presentation: We described a 17-year-old adolescent who was diagnosed with ALL and had renal involvement as the first manifestation, which was very rare in the existing studies. FISH analysis indicated a rearrangement of ZNF384 according to its probe. The patient had a typical characteristic immunophenotype of ZNF384 rearrangement, with CD10 negativity and CD13 and CD33 positivity. She had an unfavorable prognosis because she responded poorly to chemotherapy and developed a relapse shortly after reaching CR.

Conclusion: The importance of ZNF384 rearrangements in terms of prognosis remains unclear. We reported an adolescent who was diagnosed with ZNF384-rearranged ALL with renal involvement. She underwent different therapies, but her prognosis remained poor. Since ZNF384 rearrangements may act as a prognostic predictor in children or adolescents, early detection based on its characteristic immunophenotype is of great necessity.

Keywords: Acute lymphocytic leukemia; Gene rearrangement; Immunophenotype; Prognosis; ZNF384.

Fig. 1

Pathological results of kidney biopsy and bone marrow aspiration smear and results of FISH. A, B The result of kidney biopsy shows increased lymphocytes, indicating lymphoblastic lymphoma or leukemia with kidney involvement (A: HE staining; original magnification, ×400 and B: PAS staining; original magnification, ×400). C The result of Wright-Giemsa staining of the bone marrow smear sample is shown. Bone marrow hyperplasia is extremely active, with lymphoblasts accounting for 50.8% of cells before treatment (Wright-Giemsa staining; original magnification, ×1000). D Lymphoblasts were negative for myeloperoxidase (red arrow), suggesting the possible diagnosis of acute lymphocytic leukemia (POX staining; original magnification, ×1000). E Fluorescence in situ hybridization (FISH) using a ZNF384 break-apart probe shows ZNF384 rearrangement in the kidney biopsy sample. Recognizable split signals can be seen in the scattered individual cells. The white arrows represent a single red signal and a single green signal (1R1G), which are split signals. The yellow arrow represents a single yellow signal (1Y), which is a normal signal. 1R1G1Y is a positive signal model for ZNF384 rearrangement. F Describes the ZNF384 rearrangement (39%) in the bone marrow sample, indicating homology with the rearrangement of ZNF384 in the kidney biopsy sample. The two yellow arrows on the left represent two yellow signals, which are negative signals for ZNF384 rearrangement. The white arrows and the yellow arrows on the right are indicative of ZNF384 gene rearrangement (1R1G1Y)

Fig. 2

Karyotype analysis of chromosomal G-banding. The G-banded karyotype of bone marrow cells showed a normal karyotype upon admission to our hospital

Fig. 3

The results of flow cytometry. The flow cytometry results indicated acute lymphocytic leukemia. A The proportion of primary cells was 68.45% according to the SSC/CD45 gating. B The CD22 fraction is shown as 22.8%. C CD19 was positive, with a proportion of 81.1%, and CD10 was positive, with a proportion of 20.9%. D CD34 was positive, with a proportion of 98.2%, and CD13 was positive, with a proportion of 55.8%. E CD20 was positive, with a proportion of 35.0%. F CD33 was positive, with a percentage of 69.8%