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. 2022 Sep 21:9:890959.
doi: 10.3389/fmed.2022.890959. eCollection 2022.

Clinical profile in KMT2A-SEPT6- positive acute myeloid leukemia: Does it often co-occur with NRAS mutations?

Fang Chen  1 , Ying Yang  2 , Shuang Fu  1
Affiliations

Clinical profile in KMT2A-SEPT6- positive acute myeloid leukemia: Does it often co-occur with NRAS mutations?

Fang Chen et al. Front Med (Lausanne). .

Abstract

Background: The KMT2A-SEPT6 fusion gene is a relatively rare genetic event in leukemia. Its clinical characteristics and prognosis, especially the profile of co-occurring gene mutations remain unclear.

Methods: We retrospectively analyzed the characteristics of four cases carrying KMT2A-SEPT6 in our hospital, and provided a literature review.

Results: All the four patients were diagnosed with acute myeloid leukemia (AML) and harbored X chromosome and 11 chromosome rearrangements, they all manifested high levels of D-dimer. Three of four patients had NRAS mutations while one patient with congenital AML did not. Of the four cases, one developed drug resistance, one suffered relapse after bone marrow transplantation (BMT) and two died. Combined with other cases reported in the literature, we found that of all patients diagnosed with AML, 90.9% were children (≤9 years old). Patients with white blood cells ≥20.0 × 109/L or diagnosed with M4 had a shorter overall survival (P < 0.05). Age, whether to receive BMT, and the chromosome rearrangement patterns had no significant effect on overall survival (P > 0.05).

Conclusions: KMT2A-SEPT6 was more commonly observed in pediatric AML patients, some of which may co-occur with NRAS mutations. The prognosis was related to the white blood cell levels and the leukemia subtype, but was not related to age or BMT. More cases need to be accumulated to better understand the profile in KMT2A-SEPT6-positive AML.

Keywords: KMT2A-SEPT6; NRAS; acute myeloid leukemia; gene rearrangement; mutations.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Morphologic evaluation of leukemic cells at diagnosis (Wright–Giemsa stain, × 1,000). (A–D) represent cases 1, 2, 3, and 4, respectively. BM, bone marrow; PB, peripheral blood.
Figure 2
Figure 2
Flow cytometry results of bone marrow. (A–D) represent cases 1, 2, 3, and 4, respectively.
Figure 3
Figure 3
Karyotype analysis results of bone marrow. (A–D) represent cases 1, 2, 3, and 4, respectively.
Figure 4
Figure 4
Kaplan–Meier survival analysis of eighteen cases with complete follow-up information. These included fourteen reported cases with clinical follow-up and four cases in our series. (A) Overall survival of eighteen cases. (B) Infant group (≤1 year) vs. pediatric group (>1 and < 18 years old), P = 0.4632. (C) WBC count < 20.0 × 109/L vs. ≥20.0 × 109/L, P = 0.0072. (D) FAB subtype. M4 vs. M2, P = 0.0212; M4 vs. M5, P = 0.2578; M2 vs. M5, P = 0.6738. (E) Chromosomal insertion vs. chromosomal translocation, P = 0.7095. (F) Chemotherapy alone vs. BMT, P = 0.6958.
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References

    1. Culp-Hill R, D'Alessandro A, Pietras EM. Extinguishing the embers: targeting AML metabolism. Trends Mol Med. (2021) 27:332–44. 10.1016/j.molmed.2020.10.001 - DOI - PMC - PubMed
    1. Hasserjian RP. Controversies in the recent (2016) World Health Organization classification of acute myeloid leukemia. Best Pract Res Clin Haematol. (2021) 34:101249. 10.1016/j.beha.2021.101249 - DOI - PubMed
    1. Matsuo H, Yoshida K, Fukumura K, Nakatani K, Noguchi Y, Takasaki S, et al. . Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia. Blood Adv. (2018) 2:2879–89. 10.1182/bloodadvances.2018019398 - DOI - PMC - PubMed
    1. Wander P, Arentsen-Peters STCJM, Pinhan?os SS, Koopmans B, Dolman MEM, Ariese R, et al. . High-throughput drug screening reveals Pyrvinium pamoate as effective candidate against pediatric MLL-rearranged acute myeloid leukemia. Transl Oncol. (2021) 14:101048. 10.1016/j.tranon.2021.101048 - DOI - PMC - PubMed
    1. Meyer C, Burmeister T, Gröger D, Tsaur G, Fechina L, Renneville A, et al. . The MLL recombinome of acute leukemias in 2017. Leukemia. (2018) 32:273–84. 10.1038/leu.2017.213 - DOI - PMC - PubMed