Secondary clonal hematologic neoplasia following successful therapy for acute promyelocytic leukemia (APL): A report of two cases and review of the literature

Abstract

Although rare, secondary clonal hematologic neoplasia may occur after successful therapy for acute promyelocytic leukemia (APL). These secondary clonal events may be considered therapy-related, but may also be due to an underlying background of clonal hematopoiesis from which both malignancies may develop. In this manuscript, we describe two patients with secondary clones after APL therapy characterized in one patient by deletion of chromosome 11q23 and, in the other, by monosomy of chromosome 7, and also provide a review of all secondary clonal disorders described after APL therapy. We suggest that since most reports identify karyotypic abnormalities not typically associated with chemotherapy, there may be another mechanism underlying secondary clonal development after complete response to initial APL therapy.

BCR-ABL1-positive acute lymphoblastic leukemia following successful treatment of acute promyelocytic leukemia: case report

“…Since the combination of ATRA and ATO with or without chemotherapy, the survival rates of APL patients have been dramatically improved, exceeding 80%-95% (Kantarjian et al, 2021;Ferrara et al, 2022). However, some patients developed therapy-relate myeloid neoplasms (t-MN), such as therapyrelated AML or myelodysplastic syndrome (t-AML/MDS), with an incidence of 1%-9.8% (Gaut et al, 2018). And others developed secondary solid tumors (Huang et al, 2001;Au et al, 2007;Eghtedar et al, 2015).…”

PRMT5-Mediated RNF4 Methylation Promotes Therapeutic Resistance of APL Cells to As2O3 by Stabilizing Oncoprotein PML-RARα

“…PML-RARα degradation is a SUMO-triggered and RNF4/ubiquitination-mediated process [12,13]. However, this therapeutic scheme may cause serious side events such as systemic infection and secondary leukemia [14,15]. In addition, some APL patients fail to respond to therapy targeting PML-RARα or relapse after a complete remission [16][17][18].…”

A novel KMT2A–USO1 fusion gene‐induced de novo secondary acute myeloid leukaemia in a patient initially diagnosed with acute promyelocytic leukaemia

“…The question whether secondary acute myeloid leukaemia (sAML) originates from a newly acquired or pre-existing clone has not been resolved for decades. Most cases of sAML are generally considered as therapy-related leukaemia, 1 especially those with chromosomal translocations at 11q23 that involve the KMT2A gene (also known as MLL). 2,3 Here, we describe a 62-year-old male who was initially diagnosed with acute promyelocytic leukaemia (APL) carrying t(15;17)(q24;q21)/PML-RARa.…”