Novel fusion between the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with chronic myeloid leukemia-like neoplasm: undetectable residual disease after imatinib therapy.
Rare patients suffering from myeloid neoplasms share clinical and cytological features indistinguishable from chronic myeloid leukemia (CML) but lack the BCR-ABL1 fusion gene. Several studies provide evidence that alterations in genes encoding tyrosine kinase receptors such as the platelet-derived growth factor receptor (PDGFR) may be involved in the pathogenesis of these disorders. Here we describe a patient with a rare CML-like disease in whom we identified a novel in-frame BCR-PDGFRA rearrangement joining BCR exon 17 to PDGFRA exon 13, resulting in overexpression of PDGFRA. The design of a specific quantitative PCR assay to monitor the molecular response during treatment with imatinib, a multitargeted tyrosine kinase inhibitor (TKI) with activity against ABL, c-Kit, and PDGFRA revealed an outstanding disease control with durably undetectable BCR-PDGFRA transcripts. Multiple TKIs are currently available yet with distinct target profiles; thus, accurate molecular diagnosis and monitoring tools are essential to establish tailored treatments and assess response to therapy in this type of rare hematological malignancy.
Service d'Hématologie adulte, Hôpital Saint Louis, AP-HP, Paris, France.|Centre Méditerranéen de Medecine Moléculaire, INSERM U1065, Nice, France.
Thomas
T
Cluzeau
Laboratoire d'Hématologie, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France.
Eric
E
Lippert
Laboratoire d'hématologie, Hôpital Saint Louis, Université Paris Diderot, AP-HP, Paris, France.|EA3518, University Paris Diderot, Paris, France.
Jean-Michel
JM
Cayuela
Laboratoire de Cytogénétique, Hôpital Saint Louis, AP-HP, Paris, France.
Odile
O
Maarek
Laboratoire d'Hématologie, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France.
Marina
M
Migeon
Laboratoire Central d'Hématologie, Hôpital Saint Louis, AP-HP, Paris, France.
Maria-Elena
ME
Noguera
Service d'Hématologie adulte, Hôpital Saint Louis, AP-HP, Paris, France.|Laboratoire d'hématologie, Hôpital Saint Louis, Université Paris Diderot, AP-HP, Paris, France.
Hervé
H
Dombret
Service d'Hématologie adulte, Hôpital Saint Louis, AP-HP, Paris, France.|Laboratoire d'hématologie, Hôpital Saint Louis, Université Paris Diderot, AP-HP, Paris, France.
Delphine
D
Rea
D000368:Aged; D005091:Exons; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr / Q000096:biosynthesis / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr
BCR-PDGFRA; imatinib; myeloproliferative disorder