High-risk cytogenetic abnormalities (HRCAs) influence the prognosis of multiple myeloma (MM). However, additional cytogenetic aberrations can lead to poor outcomes. This study aimed to clarify whether HRCAs and additional chromosomal abnormalities affect MM prognosis. Patients with newly diagnosed MM who were treated with novel agents were retrospectively evaluated. The primary objective was to assess the difference in progression-free survival (PFS) and overall survival (OS) between patients with/without HRCAs and between patients with/without complex karyotype (CK). The secondary objectives were to identify factors affecting PFS/OS and factors related to CK. HRCAs were defined as del(17p), t(4;14), t(14;16), and gain/amplification(1q) assessed using fluorescence in situ hybridization. CK was defined as ≥3 chromosomal abnormalities on G-banding. Among 110 patients, 40 had HRCAs and 15 had CK. In this study, survival durations between patients with/without HRCAs were similar, while the CK group had significantly poorer PFS/OS than the no-CK group (median PFS: 9 vs. 24 months and median OS: 29 vs. 97 months, respectively), and a poor prognostic impact of CK was maintained in patients with HRCAs. In multivariate analysis, CK was correlated with poor PFS/OS (hazard ratio [HR]: 2.39, 95% confidence interval [95% CI]: 1.22-4.66 and HR: 2.66, 95% CI: 1.10-6.45, respectively). Bone marrow plasma cell (BMPC) ≥60% (odds ratio [OR] = 6.40, 95% CI: 1.50-27.2) and Revised International Staging System III (OR = 7.53, 95% CI: 2.09-27.1) were associated with CK. Our study suggests that CK may contribute to the poor prognosis of MM. Aggressive disease status including high BMPC proliferation could be relevant to CK.

Acute promyelocytic leukemia (APL) is a type of myeloid leukemia with a specific chromosomal translocation t(15;17)(q22; q12) forming the PML-RARA fusion gene. However, approximately one third of newly diagnosed patients with APL have additional chromosomal abnormalities. Here, we report a case of APL with co-existence of a novel translocation t(7;12)(q32;q13) involving an out-of-frame fusion between EXOC4 and TRHDE, together with PML-RARA. The patient achieved complete remission after treatment with conventional therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Although the causative link between EXOC4-TRHDE and PML-RARA has yet to be established, the patient had a good response to therapy, suggesting that the EXOC4-TRHDE fusion does not affect the efficacy of combined treatment with ATRA and ATO.

Despite the major advancements in the management of chronic phase (CP) chronic myeloid leukemia (CML), blast crisis (BC) remains a major therapeutic challenge. BC can be myeloid, lymphoid, or mixed lineage with myeloid BC being the most common type. BC in CML is mediated by aberrant tyrosine kinase activity of the BCR::ABL fusion protein. The introduction of BCR::ABL tyrosine kinase inhibitor (TKI) has been a gamechanger in the treatment of CML and there has been a significant reduction in the incidence of BC. The main treatment goal in BC is to achieve a second CP and consolidate that with an allogeneic stem cell transplantation (SCT) in eligible patients. The outcomes in BC remain dismal even in the current era. In this review, we provide an overview of the biology and current therapeutic approach in myeloid BC.

Although tyrosine kinase inhibitors markedly improve the clinical outcome of chronic myeloid leukemia (CML), blast crisis in CML (CML-BC) still has a poor prognosis. Many chromosomal abnormalities have been reported in CML-BC and may contribute to therapeutic resistance, disease progression, and prognosis. Herein, we report a rare chromosome abnormality with der(16)t(1;16)(q12;q11.2) in CML-BC. It has been demonstrated that this chromosomal abnormality is associated with disease progression and poor prognosis in other malignancies, such as Ewing sarcoma. A 70-year-old man with CML who had been treated with imatinib and dasatinib was admitted to our hospital after complaining for several weeks of fatigue and dyspnea and diagnosed with CML-BC. His tumor cells presented additional chromosomal abnormality with der(16)t(1;16)(q12;q11.2), which has never been reported in CML cases. We successfully treated him using cytotoxic agents combined with ponatinib, and this chromosome abnormality was detected via G-banding. Our patient has lived for over 8 months without any progression with ponatinib treatment alone. Although the biological function of this chromosomal abnormality remains unclear, the satellite DNA of 1q12, which induces genomic instability in other malignancies, and the loss of 16q may contribute to the disease progression of CML in this case. In conclusion, this paper is the first to report on the case of CML-BC with der(16)t(1;16)(q12;q11.2).

In this review, we emphasize up-to-date practical cytogenetic and molecular aspects of chronic myeloid leukemia (CML) and summarize current knowledge on tyrosine kinase inhibitor (TKI) resistance and treatment response monitoring of CML.
The introduction of TKIs has changed the natural course of CML and markedly improved patient survival. Over the past decades, many research efforts were devoted to elucidating the leukemogenic mechanisms of BCR-ABL1 and developing novel TKIs. More recent studies have attempted to answer new questions that have emerged in the TKI era, such as the cytogenetic and molecular bases of treatment failure and disease progression, the clinical impact of genetic aberrations in Philadelphia chromosome (Ph)-positive and Ph-negative cells, and the biological significance of Ph secondarily acquired during therapy of other hematological neoplasms. Recent progresses in the understanding of the cytogenetic and molecular mechanisms underlying therapeutic failure and disease progression have improved the risk stratification of CML and will be helpful in the design of novel therapeutic strategies.

暂无摘要。

In Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), additional chromosomal abnormalities (ACAs) are frequently observed. We investigated the cytogenetic characteristics and prognostic significance of ACAs in Ph-positive ALL. We reviewed the clinical data and bone marrow cytogenetic findings of 122 adult Ph-positive ALL patients. The ACAs were examined for partial or whole chromosomal gains or losses, and structural aberrations. The overall survival (OS) and disease-free survival (DFS) of patients who received hematopoietic cell transplantation were compared between the isolated Ph group and ACA group. ACAs were present in 73.0% of all patients. The recurrent ACAs were extra Ph (24.7%), 9/9p loss (20.2%), and 7/7p loss (19.1%). Complex karyotype was found in 28.1% of patients in the ACA group. Younger patients (19-30 years) in the ACA group showed the highest frequency of extra Ph (54%) compared to other age groups. The OS in the ACA group was significantly shorter than in the isolated Ph group. The presence of an extra Ph chromosome or 9/9p loss was significantly associated with shorter OS and DFS, whereas 7/7p loss and complex karyotype were not associated with poorer prognosis. We suggest that subclassification of ACAs could be applied to prognostic investigation of Ph-positive ALL.