A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation

Abstract

Hematopoietic myeloproliferative neoplasms with FGFR1 rearrangement result in the 8p11 myeloproliferative syndrome that in the current Word Health Organization classification is designated as “myeloid and lymphoid neoplasm with FGFR1 abnormalities.” We report the case of a 66-year-old man who had clinical features that resembled chronic myeloid leukaemia (CML), but bone marrow cytogenetic and fluorescent in situ hybridization (FISH) studies showed t(8;22)(p11;q11) and BCR-FGFR1 fusion gene. He was initially managed with hydroxyurea, and given the aggressive nature of this disease, four months later, the patient underwent an allogeneic hematopoietic stem-cell transplantation (HSCT) from an HLA-haploidentical relative. Currently, HSCT may be the only therapeutic option for long-term survival at least until more efficacious tyrosine kinase inhibitors (TKIs) become available.

A case mimicking chronic myeloid leukemia with t(8;22)(p11;q11)/BCR-FGFR1 and sequential transformation to B-acute lymphoblastic leukemia and acute myeloid leukemia

“…As for that, in 2016 WHO classification, myeloid/lymphoid neoplasm was identified according to rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 [14]. Among these, myeloid/lymphoid neoplasm with rearrangement of FGFR1 gene is quite rare [5][6][7]15]. Due to clinical and laboratory features similar to CML, these patients are usually misdiagnosed.…”

“…FGFR1 gene has many fusion partner genes; the most frequent is the BCR gene. This new fusion protein activates tyrosine kinases and induces development of several hematologic malignancies [5]. Patients with FGFR1-BCR fusion transform frequently to AML and infrequently to ALL and lymphoid neoplasms after a short period of chronic phase [2].…”

“…Patients carrying the BCR-FGFR1 fusion gene develop resistance to chemotherapy or TKIs treatments. However, it was reported that those patients may benefit from treatment with multi-tyrosine kinase inhibitors (e.g., ponatinib) [5,15], FGFR1 inhibitors [3,19], or allogeneic SCT [1].…”

“…Translocation between chromosomes 8 and 22 leads to the formation of a protein similar to the BCR/ABL chimeric protein [3,4]. Accordingly, the clinical features of the patients with BCR-FGFR1 fusion gene are similar to chronic myeloid leukemia (CML) and thus may be misdiagnosed as CML [5][6][7]. These patients are resistant to tyrosine kinase inhibitor (TKI) therapy, so they are generally treated with chemotherapy and allogeneic stem cell transplantation (SCT).…”

Identification of a novel HOOK3-FGFR1 fusion gene involved in activation of the NF-kappaB pathway

“…These patients are resistant to current therapeutic regimens including tyrosine kinase inhibitors (TKIs) and have a 5-year survival rate of < 20% [ 2 , 3 ]. Currently, allogeneic hematopoietic stem-cell transplantation is the only potentially curative therapeutic option to prolong survival [ 3 , 4 ]. Thus, there is an urgent need for alternative treatment plans for patients who are either awaiting or unable to receive transplantation.…”