A Case of 8p11 Myeloproliferative Syndrome with <b><i>BCR-FGFR1</i></b> Gene Fusion Presenting with Trilineage Acute Leukemia/Lymphoma, Successfully Treated by Cord Blood Transplantation

Abstract

The 8p11 myeloproliferative syndrome is a rare neoplasm associated with chromosomal translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene located at chromosome 8p11–12. FGFR1 encodes a transmembrane receptor tyrosine kinase. The resultant fusion proteins are constitutively active tyrosine kinases that drive the proliferation of hematopoietic cells, whose uncontrolled growth can present as a myeloproliferative neoplasm. We report here the case of a 50-year-old man harboring the t(8;22)(p12;q11) chromosomal translocation in cells from both bone marrow and lymph nodes. He presented with acute leukemia and lymphoma with trilineage features. A novel mRNA in-frame fusion between exon 4 of the breakpoint cluster region (BCR) gene at chromosome 22q11 and exon 9 of FGFR1 gene on chromosome 8p11–12 was identified by reverse transcription polymerase chain reaction analysis and was confirmed by DNA sequencing. Because the patient was refractory to chemotherapy, cord blood transplantation was performed in progressive disease. It resulted in a successful outcome in which cytogenetic complete remission has been maintained for 2 years till date.

Early lesions of follicular lymphoma: a genetic perspective

“…In contrast to the situation in PFL, large fractions of both gains and losses were not found in FL grades 1-2 and/or 3A (45 to 83%, respectively, Figure 3C). Among the shared genes, a limited set of relevant amplified oncogenes (BCL2, BCL6, FGFR1, EIF4A2 and TFRC) and deleted tumor suppressors (PTEN, FAS, and TP73) could nevertheless be identified; some of them were also shared with the other FLIS/PFL entities (BCL2, BCL6, TP73, Online Supplementary Table S3), previously reported to be altered in non-Hodgkin lymphoma (BCL2, BCL6, TFRC, and TP73) 33,37 and/or highly increased transcriptionally in FL samples compared to in normal B-cell subsets (EIF4A2, TFRC, Online Supplementary Figure S5C and Online Supplementary Table S3). Furthermore, recurrent deletion of chromosome 1p was again observed, encompassing the same TNFR family members previously identified in PFL and FL, as well as a high mutation load of TNFRSF14 exons (Online Supplementary Figure S6B and Online Supplementary Table S4).…”

A case of acute myelogenous leukaemia characterised by the BCR-FGFR1 translocation

“…This implies that BCR and subsequently all the partner genes may have a role in the pathogenesis of the disease, each resulting in a distinct malignant phenotype 7. Furthermore, the biphenotypic nature of the disease supports the hypothesis that the cell of origin in EMS is a pluripotent stem cell 8. Contrary to previous cases, our patient presented with AML without a documented CML-like phase and she did not harbour chromosomal abnormalities that disrupt RUNX1, as was the case with two cases that progressed to AML.…”

Chronic myelogenous leukemia-like hematological malignancy with t(8;22) in a 26-year-old pregnant woman: A case report

“…Of the 15 patients with laboratory data, 13 patients showed an increased WBC count (median, 5.56x10 10 /l; range, 1.84-19.8x10 10 /l), while the remaining 2 displayed a normal and a decreased WBC count of 5.1x10 9 /l (13) and 1.5x10 9 /l (16), respectively. Among the 15 cases, 10 displayed a decreased Hb level (median, 108 g/l; range, 72-131 g/l) (4,5,(9)(10)(11)(13)(14)(15)(16)(17), and the majority of these cases exhibited a marginal decrease in Hb levels. While 2 out of the 15 patients showed increased Plt levels (9,13), decreased levels were observed in 4 cases (11,(14)(15)(16) and the remaining 9 displayed normal levels.…”

“…Since the first case reported by Fioretos in 2001 (5), to the best of our knowledge, t(8;22)(p11;q11) has been reported in only 17 cases with hematological malignancies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Of these, 6 cases presented with atypical CML (2-4,6,7), 3 with myeloproliferative neoplasms (5,8,9), 3 with B-cell acute lymphoblastic leukemia (10-12) and 5 with other types of hematological neoplasms (13)(14)(15)(16)(17). t(8;22) results in an in-frame fusion of FGFR1 on 8p11 and BCR on 22q11, and causes constitutive activation of the tyrosine kinase of the breakpoint cluster region/fibroblast growth factor receptor 1 (BCR/FGFR1) chimera protein, similar to Abelson murine leukemia viral oncogene homolog 1 (ABL) kinase activity in the BCR/ABL chimera (2,18).…”