Early Death in Two Patients with Acute Promyelocytic Leukemia Presenting the bcr3 Isoform, FLT3-ITD Mutation, and Elevated WT1 Level

Abstract

Despite major advances in the treatment of acute promyelocytic leukemia (APL), the problem of early death (ED) remains unsolved. Alongside the currently known clinical and hematological risk factors, prognostic significance has been attributed to internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD), hypogranular variant morphology, and the bcr-3 isoform of PML-RARα. We describe premature death of two patients with the hypogranular variant of APL who presented remarkably high expression levels of Wilms' tumor gene (WT1). Our results point to WT1 as an important prognostic factor of ED that needs to be promptly evaluated in all newly diagnosed cases of APL.

Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report

“…Our case was similar to that of Greco et al 16 Moreover, our patient presented a complex karyotype through chromosome analysis and mixed molecular expression according to flow cytometry. After treatment, our patient achieved complete remission, but unfortunately he died of pulmonary infection.…”

“…Both of them died during early treatment. 16 In addition, Zou et al 17 and Liu et al, 18 reported two cases of APL with FLT3-TKD mutation that were WT1-positive, and both of these patients suffered systemic relapse. However, neither the bcr subtype of PML-RARα nor the specific cell morphology was mentioned ( Table 1 ).…”

Outcome of PML-RARα Short Isoform and FLT3-ITD in a Patient with Several Adverse Prognostic Markers: a Case Report

“…There are only two case reports in the literature that have shown PML-RARα and FLT3-ITD in patients with poor outcome. Both the reported cases carried WT1 gene mutation and died during induction phase [5,6].…”

Favorable outcome of PML‐RARα short isoform and FLT3‐ITD mutation in a patient with several adverse prognostic markers: A case report

“…There are only two case reports in the literature that have shown short isoform of PML‐RARα and FLT3 ‐ITD mutations in patients with poor outcome. Both the reported cases carried WT1 gene mutation and died during induction phase 5,6 …”

“…Both the reported cases carried WT1 gene mutation and died during induction phase. 5,6 In the diagnostic setting, PML-RARα is detected by qPCR as three different isoforms: the long bcr-1, the variant bcr-2, and the short bcr-3. 2 Approximately, 70% of APL patients express the long/variant type PML-RARα, whereas the S type isoform is seen in ~30% of APL patients.…”