T‐cell blast crisis of chronic myelogenous leukemia presented with coexisting p210 and p190 BCR‐ABL transcripts and t(10;11)(q11;p15)

Abstract Background Blast transformation of chronic myelogenous leukemia (CML) to T lymphoblastic lymphoma/acute lymphoblastic leukemia (T‐LBL/ALL) is rare, and the molecular mechanism is still unclear. Case report A 28‐year‐old woman who developed T‐ALL with coexpressing both p210 and p190 BCR‐ABL transcripts five years after the initial diagnosis of CML in chronic phase. The proliferation of bone marrow was extremely active with blast cells over 20%. Chromosome analysis revealed t(9;22)(q34;q11) and t(10;11)(q25;p15). Flow immunophenotyping showed that blasts expressed CD4, CD7, CD11b, CD38, CD34, CD33, and cCD3. Conclusion It is the first T‐cell blast of CML case with coexisting p210 and p190 as well as additional chromosome translocations. Through review this case and previous reports, we will reveal that CML patients with T‐lymphocyte transformation depend on potential molecular and pathological mechanism.

It is not entirely clear about the molecular mechanism of CML transformation into T-LBL/ALL. Studies showed that clone evolution of BCR-ABL fusion gene and ACAs may play important roles in blastic transformation of CML. 3 Here, we discussed the potential molecular mechanisms of CML to T-cell blast by reviewing an unusual case of coexpressing p210 and p190 as well as aberration of chromosome 11p15.

| C A S E DE SCRIP TI ON
A 24-year-old woman was initially identified as CML for bone marrow (BM) smear image, cytogenetic karyotype 46, XX, t(9;22)(q34;q11) ( Figure 1A), and the BCR/ABL (p210) fusion transcript ( Figure 2A) by reverse transcriptase-polymerase chain reaction (RT-PCR). She was treated with hydroxyurea (the specific dose is unknown). Three years F I G U R E 1 G-banding karyotype of bone marrow in chronic phase (A) and blast crisis (B). Red arrow: t(9;22)(q34;q11.2), blue arrow: t(10;11)(q11;p15) F I G U R E 2 The agarose gel electrophoresis picture of BCR-ABL fusion gene at diagnosis (A) and in blast crisis (B). The case is from the patient sample, and b3a2 (p210) is 319bp, while e1a2 (p190) is 378bp. PC, positive control; NC, negative control; the molecular weight marker is shown at right end (A) and middle (B), respectively. Unlabeled lanes are BCR-ABL fusion gene amplification bands from other patients later, the patient presented with masses in the bilateral mandibular without fever. BM smear and karyotype indicated CML was in chronic phase. But p210 was still replicated with 163 copies/95117 ABL copies.

| D ISCUSS I ON
The terminal phase of CML is usually transformed into acute myeloid leukemia (AML) and a few B acute lymphoblastic leukemia (B-ALL), rarely involving T-lineage in clinical practice. Up to now, only a limited number of CML cases with T-cell blast (52 cases) were reported. 2,[4][5][6][7] We reviewed these documents including a case of admission to our hospital, which clinical materials were summarized as follows: 52 patients with a median age of 41.5 (12-72 years), male:female = 38:14.
Extramedullary involvement was more common (34/52). In this case, the women presented with multiple masses of the neck and immunophenotype showed BM had been affected. Owing to lack of FISH and pathological biopsy results of lymph nodes, we cannot prove exactly whether extramedullary had been blasted before bone marrow involvement. RT-PCR results showed that 13 of 15 cases were M-bcr (p210) type and 2 cases with m-bcr (p190). It is generally believed that BCR/ABL fusion gene transcripts in CML are mainly M-bcr (p210), while m-bcr (p190) is dominant in Ph + ALL. The coexpression of p210 and p190 were reported rarely in B-cell CML-BC and Ph + T-ALL, 2,8 but the T-cell BC of CML has not been reported.
Surprisingly, both p210 and p190 appeared simultaneously during the CML-BC in our case. It has been confirmed p190 has stronger tyrosine kinase activity and transformation potential than p210.
Studies showed that CML patients with the p190 transcript are more likely to present in BP initially and a tendency to progress to lymphoid blast. 9,10 Most blasting CML patients (about 70%) have additional chromosomal abnormalities, which were associated with worse effect for therapy, the adverse prognosis, blasting more easily, and shorter overall survival (OS). 11,12 The most common aberrations, such as +8, 2Ph, and i (17q), have been recognized as independent indicators of the progress of CML. 13,14 In some and T-ALL. 15 Among these, NUP98-RAP1GDS1 and NUP98-ADD3 fusion genes resulting from t(4;11)(q21;p15) and t(10;11) (q11;p15), respectively, are most closely related to T-ALL. 16,17 Reciprocal translocation of chromosomes 10 and 11 t(10;11) (q11;p15) was found in our case. Although the breakpoints of chromosome 10 in our case are different from previous report,

| CON CLUS ION
In summary, our report broadens the spectrum of T cell of CML-BC and provides useful molecular evidence to support the presence of m-bcr transcript, and chromosome 11p15 is crucial for T-LBL/ALL from blast crisis of CML.

E TH I C S S TATEM ENT
The authors have no ethical disclosures to declare.