A novel cryptic CBFB-MYH11 gene fusion present at birth leading to acute myeloid leukemia and allowing molecular monitoring for minimal residual disease

P. J. Poddighe, M. A. Veening, M. B. Mansur, A. H. Loonen, T. M. Westers, P. A. Merle, J. W. Wessels, V. de Haas, W. A. Kors, S. L. Bhola, M. J. Wondergem, A. M. Ford, G. J.L. Kaspers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Acute myeloid leukemia (AML) with the inv(16)/t(16;16) karyotype is associated with a favourable prognosis, showing longer periods of complete remission and high overall survival rates. Here we report a four year old girl, who presented with pallor, a history of viral infections and pancytopenia, an abnormal karyotype, but initially no signs of leukemia. After one month, molecular diagnostics revealed a rare CBFB/MYH11 fusion variant transcript type S/I, leading to the diagnosis of CBF AML. Additional FISH confirmed the presence of a cryptic CBFB/MYH11 fusion. We developed a nested PCR test for the CBFB/MYH11 fusion gene transcript S/I to monitor this patient for minimal residual disease. Eleven months after complete remission this transcript was still absent in peripheral blood samples. Because at presentation this girl had no clinical signs of leukemia, but showed an abnormal karyotype with a cryptic CBFB-MYH11-fusion, we investigated whether this fusion was already present at birth. Therefore, the DNA fusion junction was cloned from diagnostic DNA and the patient-specific sequence was used to investigate the neonatal blood spot. Remarkably, the type S/I transcript of CBFB/MYH11 was present in the neonatal blood spot, most likely being the first hit in leukemogenesis.

Original languageEnglish
Pages (from-to)34-38
Number of pages5
JournalHuman Pathology: Case Reports
Volume11
DOIs
Publication statusPublished - 1 Mar 2018

Cite this

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title = "A novel cryptic CBFB-MYH11 gene fusion present at birth leading to acute myeloid leukemia and allowing molecular monitoring for minimal residual disease",
abstract = "Acute myeloid leukemia (AML) with the inv(16)/t(16;16) karyotype is associated with a favourable prognosis, showing longer periods of complete remission and high overall survival rates. Here we report a four year old girl, who presented with pallor, a history of viral infections and pancytopenia, an abnormal karyotype, but initially no signs of leukemia. After one month, molecular diagnostics revealed a rare CBFB/MYH11 fusion variant transcript type S/I, leading to the diagnosis of CBF AML. Additional FISH confirmed the presence of a cryptic CBFB/MYH11 fusion. We developed a nested PCR test for the CBFB/MYH11 fusion gene transcript S/I to monitor this patient for minimal residual disease. Eleven months after complete remission this transcript was still absent in peripheral blood samples. Because at presentation this girl had no clinical signs of leukemia, but showed an abnormal karyotype with a cryptic CBFB-MYH11-fusion, we investigated whether this fusion was already present at birth. Therefore, the DNA fusion junction was cloned from diagnostic DNA and the patient-specific sequence was used to investigate the neonatal blood spot. Remarkably, the type S/I transcript of CBFB/MYH11 was present in the neonatal blood spot, most likely being the first hit in leukemogenesis.",
keywords = "AML, CBFB-MYH11 fusion gene, Cytogenetics, MRD, Neonatal blood spot, RT-PCR",
author = "Poddighe, {P. J.} and Veening, {M. A.} and Mansur, {M. B.} and Loonen, {A. H.} and Westers, {T. M.} and Merle, {P. A.} and Wessels, {J. W.} and {de Haas}, V. and Kors, {W. A.} and Bhola, {S. L.} and Wondergem, {M. J.} and Ford, {A. M.} and Kaspers, {G. J.L.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.ehpc.2017.09.001",
language = "English",
volume = "11",
pages = "34--38",
journal = "Human Pathology: Case Reports",
issn = "2214-3300",
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TY - JOUR

T1 - A novel cryptic CBFB-MYH11 gene fusion present at birth leading to acute myeloid leukemia and allowing molecular monitoring for minimal residual disease

AU - Poddighe, P. J.

AU - Veening, M. A.

AU - Mansur, M. B.

AU - Loonen, A. H.

AU - Westers, T. M.

AU - Merle, P. A.

AU - Wessels, J. W.

AU - de Haas, V.

AU - Kors, W. A.

AU - Bhola, S. L.

AU - Wondergem, M. J.

AU - Ford, A. M.

AU - Kaspers, G. J.L.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Acute myeloid leukemia (AML) with the inv(16)/t(16;16) karyotype is associated with a favourable prognosis, showing longer periods of complete remission and high overall survival rates. Here we report a four year old girl, who presented with pallor, a history of viral infections and pancytopenia, an abnormal karyotype, but initially no signs of leukemia. After one month, molecular diagnostics revealed a rare CBFB/MYH11 fusion variant transcript type S/I, leading to the diagnosis of CBF AML. Additional FISH confirmed the presence of a cryptic CBFB/MYH11 fusion. We developed a nested PCR test for the CBFB/MYH11 fusion gene transcript S/I to monitor this patient for minimal residual disease. Eleven months after complete remission this transcript was still absent in peripheral blood samples. Because at presentation this girl had no clinical signs of leukemia, but showed an abnormal karyotype with a cryptic CBFB-MYH11-fusion, we investigated whether this fusion was already present at birth. Therefore, the DNA fusion junction was cloned from diagnostic DNA and the patient-specific sequence was used to investigate the neonatal blood spot. Remarkably, the type S/I transcript of CBFB/MYH11 was present in the neonatal blood spot, most likely being the first hit in leukemogenesis.

AB - Acute myeloid leukemia (AML) with the inv(16)/t(16;16) karyotype is associated with a favourable prognosis, showing longer periods of complete remission and high overall survival rates. Here we report a four year old girl, who presented with pallor, a history of viral infections and pancytopenia, an abnormal karyotype, but initially no signs of leukemia. After one month, molecular diagnostics revealed a rare CBFB/MYH11 fusion variant transcript type S/I, leading to the diagnosis of CBF AML. Additional FISH confirmed the presence of a cryptic CBFB/MYH11 fusion. We developed a nested PCR test for the CBFB/MYH11 fusion gene transcript S/I to monitor this patient for minimal residual disease. Eleven months after complete remission this transcript was still absent in peripheral blood samples. Because at presentation this girl had no clinical signs of leukemia, but showed an abnormal karyotype with a cryptic CBFB-MYH11-fusion, we investigated whether this fusion was already present at birth. Therefore, the DNA fusion junction was cloned from diagnostic DNA and the patient-specific sequence was used to investigate the neonatal blood spot. Remarkably, the type S/I transcript of CBFB/MYH11 was present in the neonatal blood spot, most likely being the first hit in leukemogenesis.

KW - AML

KW - CBFB-MYH11 fusion gene

KW - Cytogenetics

KW - MRD

KW - Neonatal blood spot

KW - RT-PCR

UR - http://www.scopus.com/inward/record.url?scp=85033672511&partnerID=8YFLogxK

U2 - 10.1016/j.ehpc.2017.09.001

DO - 10.1016/j.ehpc.2017.09.001

M3 - Article

VL - 11

SP - 34

EP - 38

JO - Human Pathology: Case Reports

JF - Human Pathology: Case Reports

SN - 2214-3300

ER -