Peripheral blood

Peripheral blood

Date of diagnosis: April 24, 2025

Adenopathy: Yes

Splenomegaly: Yes

B Symptoms: Yes

WBC (10⁹/L): 304 (Lymphocytes: 80%)

Hemoglobin (g/dl): 11.2

Hematocrit: 34.2

Platelets (10⁹/L): 136

LDH (UI/L): 626

B₂M (µg/mL): 2.4

Albumin (mg/dL): 3.4

Immunophenotype:  CD45+,CD19+d, CD20+d,CD5+,CD23+,CD38-,CD10-,CD200+.CD3-/+, lambda light chain restriction (dim)

Bone marrow biopsy: diffuse infiltration (95%) of small lymphoid cells co-expressing CD20, CD23 and CD5. 

Oligo DSP30 plus Pokeweed Mitogen

G-banding

45∼46,X,-Y,del(2)(p23),inv(6)(p25q13),+8,der(8)t(1;8)(q21;q24),del(10)(q24),del(14)(q24)[cp25]

OLE13q14 D13S319 -  Negative

EN12 (centromeric 12)- Negative

OLE11q22 ATM - Negative

OLE17p13 TP53 - Negative

OBA14q32 IGH nuc ish (IGHx1) [87/100]

OBA 8q24 C-MYC nuc ish (MYCx3)[70/200]/(MYCx4)[20/200]

(LiVE-LEXEL, Argentina)

  IGHV mutational status analysis:

Peripheral blood analysis of IGHV-IGHD-IGHJ regions performed by RT-PCR and bidirectional Sanger sequencing revealed an unmutated status (100% identity to germline) with an IGHV1-69*01, IGHD3-3*01 and IGHJ6*03 rearrangement.

cyclophosphamide: July2, 2025   No response

rituximab + bendamustine: July 22, 2025  No response

Ibrutinib:  November 3, 2025  Partial response

9 months

   Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. The clinical course varies widely and is associated to a number of genetic alterations. Among them, complex karyotypes (CK), particularly those with ≥5 chromosome alterations (CAs) have demonstrated to have adverse prognosis, independently of other biomarkers.

We present a CLL patient at diagnosis who exhibit a very CK with both new and infrequent CAs and a clear clonal evolution. Interestingly, the patient showed one CA not previously described in CLL: der(8)t(1;8)(q21;q24) (Mitelman Database, 2025), and two abnormalities: inv(6)(p25q13) and del(2)(p23), which have been reported only once in this pathology, both as part of a CKs (Costa et al, 2022; Fleischman et al, 1989). In addition, we also found a del(10)(q24), previously observed in ten CLL cases, eight of them with CK, and del(14)(q24), a relatively common anomaly in this entity (Mitelman Database, 2025).

FISH analysis using the CLL panel did not find alterations, but the evaluation with the MYC Break Apart probe (OBA 8q24, LiVE-LEXEL, Argentina) showed 35% cells with three normal 8q24 signals, supporting the presence of trisomy 8 involving MYC gene gain. The literature shows 51 CLL patients with trisomy 8, 21.6% of them associated to structural chromosome 6 alterations (Mitelman Database, 2025). On the other hand, the presence of MYC gains is highly infrequent in CLL. It was observed in about 0.5% by chromosome banding and 3-4% by microarrays analysis (Haferlach et al 2007; Rinaldi et al, 2011; Brown et al, 2012), and was significantly associated to CKs and adverse prognosis (Rinaldi et al, 2011; Heerema et al, 2021; Nguyen-Khac, 2022).

Acknowledgements

This study was supported by grants from: CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas) (PID Nº 1122015 0100753) and Fundación Florencio Fiorini, Buenos Aires, Argentina.