Skip to main content

Advertisement

SpringerLink
Log in

3′CBFB deletion in CBFB-rearranged acute myeloid leukemia retains morphological features associated with inv(16), but patients have higher risk of relapse and may require stem cell transplant

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Fluorescence in situ hybridization analysis (FISH) using a CBFB breakapart probe is widely used to detect CBFB rearrangement (CBFBr) in cases of acute myeloid leukemia (AML). However, detection of 3′CBFB deletion (3′CBFBdel) often poses a challenge for interpretation, and the clinical importance of 3′CBFBdel associated CBFBr remains largely unknown. We identified 16 AML patients with 3′CBFBdel, 11 (69%) of which were confirmed to have CBFB::MYH11 fusion. These 11 patients presented with de novo AML; 10 showed myelomonocytic differentiation, 8 had a prominent eosinophilic component, and 7 showed characteristic eosinophils with basophilic granules. Next generation sequencing showed mutations in 7/8 patients, 5 with KRAS/NRAS, 3 with FLT3-TKD, but none with KIT mutations. Except for one patient who died 5 days after diagnosis of AML, all 10 patients received chemotherapy and achieved remission initially. However, within 3 years, 5 (50%) patients had relapsed, of whom, 1 died and 4 received hematopoietic stem cell transplant. After a median follow-up of 76 months, 3 patients died and 8 were alive in complete remission. Our study shows that detection of 3′CBFBdel is not equivalent to unbalanced CBFB rearrangement, and therefore, an alternative confirmatory test is warranted. AML with 3′CBFBdel/CBFBr often shows similar pathological features to AML with inv(16), but appears to have different mutation profiles and a higher risk of relapse requiring hematopoietic stem cell transplant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Le Beau MM et al (1983) Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. a unique cytogenetic-clinicopathological association. N Engl J Med 309(11):630–636

    Article  Google Scholar 

  2. Marlton P et al (1995) Molecular characterization of 16p deletions associated with inversion 16 defines the critical fusion for leukemogenesis. Blood 85(3):772–779

    Article  CAS  Google Scholar 

  3. Liu P et al (1993) Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science 261(5124):1041–1044

    Article  CAS  Google Scholar 

  4. Batanian JR, Huang Y, Fallon R (2000) Deletion of 3′-CBFB gene in association with an inversion (16)(p13q22) and a loss of the Y chromosome in a 2-year-old child with acute myelogenous leukemia-M4. Cancer Genet Cytogenet 121(2):216–219

    Article  CAS  Google Scholar 

  5. Dohner H et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447

    Article  Google Scholar 

  6. Borthakur G et al (2014) Gemtuzumab ozogamicin with fludarabine, cytarabine, and granulocyte colony stimulating factor (FLAG-GO) as front-line regimen in patients with core binding factor acute myelogenous leukemia. Am J Hematol 89(10):964–968

    Article  CAS  Google Scholar 

  7. Burnett AK et al (2013) Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. J Clin Oncol 31(27):3360–3368

    Article  CAS  Google Scholar 

  8. Borthakur G, Kantarjian H (2021) Core binding factor acute myelogenous leukemia-2021 treatment algorithm. Blood Cancer J 11(6):114

    Article  Google Scholar 

  9. Borthakur G et al (2008) Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival. Cancer 113(11):3181–3185

    Article  Google Scholar 

  10. Hospital MA et al (2014) Core-binding factor acute myeloid leukemia in first relapse: a retrospective study from the French AML Intergroup. Blood 124(8):1312–1319

    Article  CAS  Google Scholar 

  11. Kadkol SS et al (2004) Comprehensive analysis of CBFbeta-MYH11 fusion transcripts in acute myeloid leukemia by RT-PCR analysis. J Mol Diagn 6(1):22–27

    Article  CAS  Google Scholar 

  12. van Dongen JJ et al (1999) Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted action: investigation of minimal residual disease in acute leukemia. Leukemia 13(12):1901–28

    Article  Google Scholar 

  13. Kelly J et al (2005) 3′CBFbeta deletion associated with inv(16) in acute myeloid leukemia. Cancer Genet Cytogenet 162(2):122–126

    Article  CAS  Google Scholar 

  14. Dawson AJ et al (2011) Inversion and deletion of 16q22 defined by array CGH, FISH, and RT-PCR in a patient with AML. Cancer Genet 204(6):344–347

    Article  CAS  Google Scholar 

  15. Egan N et al (2004) Deletion of CBFB in a patient with acute myelomonocytic leukemia (AML M4Eo) and inversion 16. Cancer Genet Cytogenet 154(1):60–62

    Article  CAS  Google Scholar 

  16. Hung D et al (2007) Deletion of 3′CBFbeta in an inv(16)(p13.lq22) ascertained by fluorescence in situ hybridization and reverse-transcriptase polymerase chain reaction. Cancer Genet Cytogenet 172(1):92–4

    Article  CAS  Google Scholar 

  17. Kolomietz E et al (2001) Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis. Blood 97(11):3581–3588

    Article  CAS  Google Scholar 

  18. Lv L, Yu J, Qi Z (2020) Acute myeloid leukemia with inv(16)(p13.1q22) and deletion of the 5′MYH11/3′CBFB gene fusion: a report of two cases and literature review. Mol Cytogenet 13:4

    Article  CAS  Google Scholar 

  19. Spencer DV et al (2007) Inverted and deleted chromosome 16 with deletion of 3’CBFB identified by fluorescence in situ hybridization. Cancer Genet Cytogenet 179(1):82–84

    Article  CAS  Google Scholar 

  20. Tirado CA et al (2010) Acute myeloid leukemia with inv(16) with CBFB-MYH11, 3′CBFB deletion, variant t(9;22) with BCR-ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review. Cancer Genet Cytogenet 200(1):54–59

    Article  CAS  Google Scholar 

  21. Tang G et al (2021) Myeloid/lymphoid neoplasms with FLT3 rearrangement. Mod Pathol 34(9):1673–1685

    Article  CAS  Google Scholar 

  22. Yang RK, et al (2021) CBFB break-apart FISH testing: an analysis of 1629 AML cases with a focus on atypical findings and their implications in clinical diagnosis and management. Cancers (Basel). 13(21)

  23. Schlenk RF et al (2004) Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol 22(18):3741–3750

    Article  CAS  Google Scholar 

  24. Appelbaum FR et al (2006) The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. Br J Haematol 135(2):165–173

    Article  Google Scholar 

  25. Delaunay J et al (2003) Prognosis of inv(16)/t(16;16) acute myeloid leukemia (AML): a survey of 110 cases from the French AML Intergroup. Blood 102(2):462–469

    Article  CAS  Google Scholar 

  26. Paschka P et al (2006) Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a cancer and leukemia group B study. J Clin Oncol 24(24):3904–3911

    Article  CAS  Google Scholar 

  27. Paschka P et al (2013) Secondary genetic lesions in acute myeloid leukemia with inv(16) or t(16;16): a study of the German-Austrian AML Study Group (AMLSG). Blood 121(1):170–177

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX, 77030, USA

    Guilin Tang, Sa A. Wang, Gokce Toruner, Shimin Hu, Shaoying Li, Jie Xu, L. Jeffrey Medeiros & Zhenya Tang

  2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Ying Zou

  3. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Gautam Borthakur

Authors
  1. Guilin Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sa A. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gautam Borthakur
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gokce Toruner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shimin Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shaoying Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jie Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L. Jeffrey Medeiros
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zhenya Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guilin Tang.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 13 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, G., Zou, Y., Wang, S.A. et al. 3′CBFB deletion in CBFB-rearranged acute myeloid leukemia retains morphological features associated with inv(16), but patients have higher risk of relapse and may require stem cell transplant. Ann Hematol 101, 847–854 (2022). https://doi.org/10.1007/s00277-022-04767-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-022-04767-1

Keywords

Search

Navigation