inv(2)(p23q13);RANBP2::ALK fusion gene in a case of chronic myelomonocytic leukaemia

Justin CH Li,Joyce S Cheung  

Haematology Section, Department of Anatomical & Cellular Pathology, Prince of Wales Hospital, Hong Kong~Haematology Section, Department of Anatomical & Cellular Pathology, Prince of Wales Hospital, Hong Kong

This chromosome aberration is

This chromosome aberration is

Patient demographics


Clinical findings (leukemia/lymphoma)

Date of diagnosis

Sample(s) submitted for testing

Sample(s) submitted for testing
Bone Marrow

Conventional cytogenetics

Cultures set up
Mitogen used
Banding used


Karyotypic description


Provide karyogram

Figure 1. Karyotype at the time of diagnosis.

Figure 2. Inv(2)(p23q13).

Follow up


Hydroxyurea for initial cytoreduction. Intravenous (IV) azacitidine for 5 cycles in 7/2019 - 11/2019. Bone marrow exam pre-transplant in 12/2019 showed complete remission of disease.u00a0First haploidentical PBSCT from patientu2019s younger sister on 2/1/2020. Bone marrow exam post-transplant in late 1/2020 showed regenerating marrow.

Disease relapse in 3/2020 with neutropenic fever and bone marrow exam showed acute myeloid leukemia. IV cytarabine for 2 doses as cytoreduction. Decitabine + venetoclax as salvage treatment for 2 cycles in 4/2020 - 5/2020. Bone marrow exam in 5/2020 showed complete remission with incomplete hematologic recovery. Treatment was switched to IV azacitidine + venetoclax for 3 more cycles in 6/2020 - 9/2020 due to financial issue.

2nd haploidentical PBSCT from patientu2019s father on 28/10/2020. Bone marrow exam post-transplant in 11/2020 showed complete remission. Post-transplant maintenance therapy with IV azacitidine for 6 cycles in 12/2020 - 9/2021.

Leukocytosis with re-emergence of blasts and promonocytes was detected in peripheral blood in 7/2021. Hydroxyurea was added for cytoreduction in 9/2021. Treatment was switched tou00a0IV azacitidine + venetoclax since 4/11/2021 till present.

Complete remission achieved
Time post diagnosis

Conclusions and relevant comments


We describe a 24-year-old man with chronic myelomonocytic leukaemia, inv(2)(p23q13) and monosomy 7. He presented with leukocytosis and bilateral retinopathy due to leukostasis. Blood film showed leucoerythroblastic reaction with occasional blasts, monocytosis and dysplastic neutrophils. Bone marrow findings were compatible with CMML. Cytogenetic study showed clonal changes with inv(2)(p23q13) and monosomy 7. ALK1 immunostaining on trephine showed nuclear membranous staining in myeloid cells. RANBP2-ALK fusion transcript was identified by RNA transcriptome sequencing and confirmed with reverse transcriptase-PCR and Sanger sequencing. Patient had undergone allogeneic haploidentical HSCT twice, but early relapses with AML were detected on bone marrow at 3 months and 8 months after first and second transplant respectively. At the time of writing, he has been followed up for 28 months since diagnosis with stable disease upon treatment with azacitidine and venetoclax.

RANBP2-ALK fusion was initially characterized in inflammatory myofibroblastic tumors and was recurrently associated with myeloid neoplasms of myelomonocytic lineage. It is reported in 3 cases of AMML, 2 cases of JMML and 1 case of CMML, all but CMML case were associated with monosomy 7. It is also identified in a case of ALK+ DLBCL. The N-terminal leucine-rich domain of RANBP2 is postulated to mediate oligomerization of the fusion protein, leading to activation of ALK kinase domain. Myeloid neoplasms with RANBP2-ALK fusion were associated with aggressive disease and poor prognosis. Several reports suggest at least transient responses to the ALK inhibitor crizotinib in RANBP2-ALK rearranged leukaemias, which may be used as bridging therapy to allogeneic HSCT.


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Justin CH Li,Joyce S Cheung

inv(2)(p23q13);RANBP2::ALK fusion gene in a case of chronic myelomonocytic leukaemia

Atlas Genet Cytogenet Oncol Haematol. 2021-12-17

Online version:;ranbp2-alk-fusion-gene-in-a-case-of-chronic-myelomonocytic-leukaemia