The Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML)

Abstract

SummaryIn the Austrian biodatabase for chronic myelomonocytic leukemia (ABCMML) clinicolaboratory real-life data have been captured from 606 CMML patients from 14 different hospitals over the last 30 years. It is the only large biodatabase worldwide in which functional methods such as semisolid in vitro cultures complement modern molecular methods such as next generation sequencing. This provides the possibility to comprehensively study the biology of CMML. The aim of this study was to compare patient characteristics with published CMML cohorts and to validate established prognostic parameters in order to examine if this real-life database can serve as a representative and useful data source for further research. After exclusion of patients in transformation characteristics of 531 patients were compared with published CMML cohorts. Median values for age, leukocytes, hemoglobin, platelets, lactate dehydrogenase (LDH) and circulating blasts were within the ranges of reported CMML series. Established prognostic parameters including leukocytes, hemoglobin, blasts and adverse cytogenetics were able to discriminate patients with different outcome. Myeloproliferative (MP) as compared to myelodysplastic (MD)-CMML patients had higher values for circulating blasts, LDH, RAS-pathway mutations and for spontaneous myelomonocytic colony growth in vitro as well as more often splenomegaly. This study demonstrates that the patient cohort of the ABCMML shares clinicolaboratory characteristics with reported CMML cohorts from other countries and confirms phenotypic and genotypic differences between MP-CMML and MD-CMML. Therefore, results obtained from molecular and biological analyses using material from the national cohort will also be applicable to other CMML series and thus may have a more general significance.

Correlation of RAS-Pathway Mutations and Spontaneous Myeloid Colony Growth with Progression and Transformation in Chronic Myelomonocytic Leukemia—A Retrospective Analysis in 337 Patients

“…We employed data from 337 CMML patients from the ABCMML which has been shown to be a representative and useful real-life data source for biomedical research [27]. In this database, we retrospectively collected epidemiologic, hematologic, biochemical, clinical, immunophenotypic, cytogenetic, molecular and biologic data of patients with CMML from different centers.…”

“…The mutational status of CMML-related protein coding genes was determined by targeted amplicon sequencing using the MiSeq platform (Illumina, San Diego, CA, USA). Details regarding gene panel, library preparation and data processing have been reported previously [27]. To minimize the chance to capture mutations which may be associated with non-neoplastic conditions we chose a VAF cutoff of ≥20% which has been shown to provide a specificity of 86% [48].…”

“…In the "Austrian Biodatabase for Chronic Myelomonocytic Leukemia" (ABCMML) we retrospectively and prospectively collect hematological, clinical, molecular, and biological information of patients with CMML from different centers in a real world setting [27]. Due to the retrospective character of our database it contains data that are obtained from patients being in different phases of CMML evolution at the time of inclusion and subsequent follow up.…”

Micro-RNA-125a mediates the effects of hypomethylating agents in chronic myelomonocytic leukemia

“…Although some patients can be cured with high-dose chemotherapy and allogeneic hematopoietic stem cell (HSC) transplantation, the majority are diagnosed at an older age and therefore ineligible for this therapeutic approach [ 2 , 3 ]. The current gold standard for this patient collective are the hypomethylating agents (HMAs), azacitidine (Aza) and decitabine (Dec) [ 3 , 4 ]. HMAs act via inducing direct cytotoxicity on the one hand and via hypomethylation of DNA on the other hand.…”

RAF Kinase Inhibitor Protein in Myeloid Leukemogenesis

“…Another interesting MN subtype for studying RKIP expression is chronic myelomonocytic leukemia (CMML). CMML is an aggressive malignancy of the HSCs, where the malignant offspring is characterized by both increased proliferation on the one hand, and increased myelomonocytic differentiation on the other hand [64,65,66]. Additionally, CMML exhibits an inherent risk of AML transformation.…”