Treatment of STAT5b-RARA positive acute promyelocytic leukemia by Venetoclax combining with homoharringtonine, cytarabine: A case report and literature review

Abstract

Introduction: Acute promyelocytic leukemia (APL) is mostly due to the chromosome translocation t (15; 17) (q22; q12), leading to the formation of PML-RARA fusion protein. Some patients carried rare translocation involving RARA gene, who were called variant APL caused by RAR family (RARA, RARB, and RARG) and partner genes. STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL. Knowledge of STAT5b-RARA (+) APL treatment is still limited. Case report: We presented a 38-year-old female variant APL case, who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction. The patient failed to respond after four-drug combined induction chemotherapy: idarubicin, cytarabine, all trans retinoic acid, and arsenic trioxide (As 2 O 3 ). Then, the patient was re-induced with azacytidine, but still failed to achieve complete remission (CR). Next, she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR. Later, the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy. Conclusion: Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully.

Identification of concurrent STAT3::RARA and RARA::STAT5b fusions in a variant APL case

“…9 Another case was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR. 10 The signal transducer and activator of transcription (STATs) are latent cytosolic transcription factors that are activated by Janus kinase (JAK) tyrosine kinases and are involved in cellular transduction of growth factor and different cytokines and hormones. 11 The STAT protein family is named for its dual roles in transducing signal from the cytokine-receptor to the nucleus and activating gene transcription, 12 including seven highly related homologous proteins: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6.…”

“…16 So far, 18 cases with STAT5b::RARA positive APL have been reported in literature review. 10 Of them, two cases were from our center. 8,17 According to the essays describing STAT5b::RARA, we ascertained that STAT5b exon 14, 15, or 16 fused with RARA exon 3 or 4, and unexpectedly, the present case is the first variant APL harboring reciprocal RARA::STAT5b.…”

“…A case presented the role of decitabine that got a second CR after relapse 9 . Another case was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR 10 …”

“…So far, 18 cases with STAT5b::RARA positive APL have been reported in literature review 10 . Of them, two cases were from our center 8,17 .…”

Venetoclax overcomes resistance to all‐trans retinoic acid in a variant acute promyelocytic leukemia with TNRC18::RARA fusion

“…Furthermore, sporadic case reports documented the successful treatment of ATRA/ATO‐resistant variant APLs with venetoclax monotherapy or in combination with chemotherapy (Table 1). 6–10 This is the first study to report on the efficacy and possible mechanisms of venetoclax plus ATRA regimen as a differentiation induction therapy in patients with variant APL carrying TNRC18::RARA . Venetoclax in combination with ATRA possesses advantages in terms of time to CR compared to venetoclax monotherapy and safety profiles compared to venetoclax‐based chemotherapy, especially suitable for older patients who are ineligible for intensive chemotherapy.…”