Received: 20.12.2024 Accepted: 20.12.2024
B lymphocytes, by producing antibodies, are responsible for one of the two major arms of the immune response, the humoral one. In order to catch up with the constantly changing repertoire of pathogens and their new structures, B cells developed during evolution unique mechanisms involving manipulation with their genes to generate billions of receptors from a limited set of genes. Some of these mechanisms are shared with T lymphocytes, such as V-D-J gene segment rearrangement, while some are unique to B cells such as hypermutation of immunoglobulin genes. The latter mechanism occurs in the peripheral lymphatic organs upon antigen stimulation.
It has been exactly 25 years since two seminal papers published in 1999 in Blood by Damle et al. and Hamblin et al. [1, 2] clearly indicated that the mutational status of IGHV (immunoglobulin variable heavy chain genes) does matter in the biology of chronic lymphocytic leukaemia, a B-cell derived neoplasm, and represents an independent prognostic factor. In the accompanying editorial Naylor and Capra wrote: “most clinical laboratories do not have the capacity to isolate and characterise IgV gene sequences” [3].
We have come a long way since then, and fortunately this test has become the standard for all patients diagnosed with CLL. However, determination of IGHV status still remains a challenge for many labs, even those with long experience in genetic diagnostics of haematological malignancies.
In this issue of Acta Haematologica Polonica, Zawada et al. [4] address comprehensively the current methodology and reporting guidelines for IGHV mutational status in CLL. This was an eagerly awaited publication. While several laboratories in Poland have recently earned an ERIC (European Research Initiative on CLL) society certificate (or are in the process of acquiring one), many issues remain problematic. There are doubts regarding methodology and how to deal with problematic samples.
We have now two major techniques: one that employs ‘old’ Sanger sequencing, and the second being NGS (next-generation sequencing). The authors explain in detail both methods, presenting their pros and cons. Importantly, guidelines for reporting are carefully prepared and discussed, including for problematic cases.
The only topic which has not been addressed by Zawada et al. is the financial challenge, this problem now being a major one for most laboratories, namely how to carry out all the molecular and cytogenetic tests that are now mandatory in CLL, within the current financial limits.
However, this is probably a topic for a separate article, especially given that this challenge is by no means CLL-specific.
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