B-cell prolymphocytic leukemia (B-PLL)

2021-02-01   Florence Nguyen-Khac , Elise Chapiro 

1.Cytogénétique Hématologique, Service d Hématologie Biologique, Hpital Pitié-Salpêtrière, APHP,.Sorbonne Université. Centre de Recherche des Cordeliers, INSERM UMRS_1138, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Paris, France elise.chapiro@aphp.fr; florence.nguyen-khac@psl.aphp.fr
2.Cytogénétique Hématologique, Service dHématologie Biologique, Hpital Pitié-Salpêtrière, APHP,.Sorbonne Université. Centre de Recherche des Cordeliers, INSERM UMRS_1138, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Paris, France elise.chapiro@aphp.fr; florence.nguyen-khac@psl.aphp.fr

Abstract

B-cell prolymphocytic leukemia (B-PLL) is a very rare mature B-cell leukemia occurring in elderly people diagnosed when prolymphocytes comprise more than 55% of the lymphoid cells in peripheral blood. A complex karyotype, MYC gene abnormalities (translocation or more rarely gain/amplification) and 17p deletion including TP53 are frequent. The prognosis is poor.

Clinics and Pathology

Phenotype stem cell origin

There is no specific immunologic marker. The B-PLL cells strongly express surface IgM/lgD, CD19, CD20, CD22, CD79a, CD79b, and FMC7. CD5 is expressed in more than half of cases, CD23 in 20-30%, and CD200 is weakly positive or negative.

Epidemiology

Very rare. Accounting for <1% of lymphocytic leukemias. The median age at diagnosis is 65-72 years, the M:F ratio is equal. The majority of cases occurs de novo, but B-PLL secondary to chronic lymphocytic leukemia (CLL) or more rarely marginal zone lymphoma exist.

Clinics

B symptoms, marked splenomegaly, no or minimal lymphadenopathy, rapidly increasing lymphocyte count, usually >100x109/L.
Atlas Image
Figure 1. Courtesy F. Nguyen-Khac

Cytology

Prolymphocytes must represent more than 55% of lymphoid cells in peripheral blood. Prolymphocytes are medium-sized lymphoid cells with a round nucleus, moderately condensed nuclear chromatin, a prominent central nucleolus, and basophilic cytoplasm.

Treatment

No consensus of treatment. Like in CLL, first-line treatment was classically based on the presence of a TP53 aberration. Chemo-immunotherapy can be proposed in patients devoid of TP53 abnormality. In patients harboring a TP53 aberration, alemtuzumab has been used. Now, targeted therapies such as BCR pathway inhibitors (such as ibrutinib) or BCL2 inhibitors (like venetoclax) are interesting options that need evaluation. Allogeneic transplant should be considered in the rare younger patients.

Evolution

Variable clinical course. A median OS of 3 years was reported; however this was prior to the advent of immunotherapy and targeted therapies. A more recent study of 34 B-PLL reported a median overall survival of 125 months.

Prognosis

The prognosis of B-PLL is poor. Three distinct cytogenetic risk groups are described: low-risk (no MYC aberration), intermediate-risk (MYC aberration but no del17p), and high-risk (MYC aberration and del17p).
Atlas Image
Figure 2. R-banded complex karyotype: t(8;22)(q24;q11) juxtaposing MYC and IGL genes loci, trisomy 12 and trisomy 18 (Courtesy F. Nguyen-Khac and E. Chapiro)
Atlas Image
Figure 3. FISH analysis with a IGL(green)/MYC(red) probe (CYTOTEST) showing a t(8;22)(q24;q11) with IGL/MYC juxtaposition. (Courtesy F. Nguyen-Khac and E. Chapiro)
Atlas Image
Figure 4. FISH analyses with a MYC break-apart probe. A and B. Gain of two copies of MYC resulting from multiple unbalanced translocation. C . Interphasic FISH: gain of one copy of MYC. (Courtesy F. Nguyen-Khac and E. Chapiro)

Genes Involved and Proteins

Note
Next generation sequencing
The most frequently mutated genes by whole exome sequencing in a series of 16 patients were: TP53 (38%, associated with del17p), MYD88 (25%), BCOR (25%), MYC (19%), SF3B1 (19%), SETD2 (12%), CHD2 (12%), CXCR4 (12%), and BCLAF1 (12%).
Mutations
IGHV analysis: the majority of B-PLL uses the IGHV3 or IGHV4 subgroups and displayed significantly mutated IGHV genes.

Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
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4294686372019Idelalisib-rituximab induces durable remissions in TP53 disrupted B-PLL but results in significant toxicity: updated results of the UK-wide compassionate use programme.Eyre TA et al
5251256252014Aberrations of MYC are a common event in B-cell prolymphocytic leukemia.Flatley E et al
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Summary

Citation

Florence Nguyen-Khac ; Elise Chapiro

B-cell prolymphocytic leukemia (B-PLL)

Atlas Genet Cytogenet Oncol Haematol. 2021-02-01

Online version: http://atlasgeneticsoncology.org/haematological/2033/b-cell-prolymphocytic-leukemia-(b-pll)

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