BCOR Mutation and TLS-ERG Expression in Acute Myeloid Leukemia with Monoclonal Immunoglobulinemia

Acute myeloid leukemia(AML) originates from the abnormal clonal proliferation of myeloblast which often combined with clinical symptoms. Cytogenetic and molecular abnormalities are frequent in AML patience. To date, the driver genes for leukemia remain largely undiscovered. Monoclonal immunoglobulinemia is a group of diseases caused by excessive proliferation of plasma cells or immunoglobulin-producing lymphoid plasma cells and B lymphocytes. It can develop into malignant plasma cell disease. Herein, we report a AML patient was concomitant with monoclonal immunoglobulinemia, the patient was also accompanied by BCOR mutation and TLS-ERG fusion gene. A 55-year-old married female was admitted into our hospital due to repeated edema for 3 weeks. On admission, peripheral blood counts: PLT142×10^9/L, HB77g/L↓, WBC35.2×10^9/L.Bone marrow examination showed the mononuclear cell system proliferated actively, and the primitive infantile monocytes accounted for 86%. Cell morphology suggested M5b(Figure1A ). Fusion gene screening in bone marrow revealed that TLS-ERG expression. Immunophenotype of bone marrow cell:Abnormal myeloid primitive cells accounted for 96.39% of the nuclear cells,expressCD33, CD13, CD123, CD34, CD9, MPO(Figure 1D). Karyotype analysis of bone marrow cells showed in Figure 1B. Thus, AML was diagnosed. Next-generation DNA sequencing technology showed that BCOR (51.7%),PLCG1(49.9%),DIS3(48.4%),BRAF(51.6%), JAK2(45.1%) ,JAK3(49.0%) were mutated. Meanwhile, we found that Peripheral blood immunofixation electrophoresis showed that Gamma region is seen with a monoclonal light chain lambda component((Figure 1C.).Then, the patient underwent one cycle of IA(Idabisine hydrochloride 10mg d1-4, cytarabine 0.075g q12h d1-7). Twenty-five after chemotherapy onset, bone marrow examination showed that primitive and immature monocytes accounted for 3%. Chromosome become normal. Minimal residual disease(MRD):0.01%. The disease reached complete remission(CR). Peripheral blood immunofixation electrophoresis turned negative. Fusion gene detection showed that TLS-ERG turned negative. BCOR mutation was not detected by Next-generation DNA sequencing. Mutations of PLCG1,DIS3,BRAF,JAK2,JAK3 still exist. Monoclonal immunoglobulinemia and AML are both clonal diseases, but originated from different clones. This case has both malignant clones of granulocyte stem cell and malignant clones of B line, so it is worthy of discussion. By comparing CR before and after we found that while the patient's M protein turned negative, the TLS-ERG fusion gene and BCOR gene mutation also disappeared. The TLS-ERG fusion gene is formed by the rearrangement of TLS and ERG genes on chromosomes 16 and 21. The current study holds that the expression of this fusion gene indicates rapid disease progression and poor prognosis. BCOR mutations can be found in AML and often coincide with DNMT3 gene mutations, suggesting it may affect the occurrence of leukemia through epigenetics. BCOR is a newly discovered corepressor of BCL-6, which can play a supporting role when BCOR combines with DNA; when BCOR is overexpressed, it can enhance the inhibition of BCL-6. BCL-6 is highly expressed in tumor cells,it encodes transcriptional repressors which are required for the formation of germinal center and may affect apoptosis. We thinked that the monoclonal immunoglobulinemia of this patient may caused by the BCOR abnormal expression which increased the inhibitory effect of BCL-6 and affect the apoptosis of B cells, and B cells continue to secrete immunoglobulin. BCOR mutations are associated with poor prognosis. The patient with TLS-ERG fusion gene which is a poor prognosis gene.However, the BCOR gene mutation site is a non-hot spot mutation which has few clinical studies. Whether the BCOR gene mutation results in the combination of the two diseases requires further study. Acknowledgment:The research was supported by fundings of the public technology research projects of Yiwu,China (2016-S-05), the key medical discipline of Yiwu,China(Hematology,2018-2020),and the academician workstation of the Fourth Affiliated Hospital of Zhejiang University School of Medicine. Correspondence to: Dr Jian Huang, Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine. N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China. Email: [email protected] Figure 1 Disclosures No relevant conflicts of interest to declare.

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Use of α-2a-Interferon to Treat Cytogenetic Relapse of Chronic Myeloid Leukemia After Marrow Transplantation

Blood ◽

10.1182/blood.v90.7.2549 ◽

1997 ◽

Vol 90 (7) ◽

pp. 2549-2554 ◽

Cited By ~ 41

Author(s):

Celestia S. Higano ◽

Deborah Chielens ◽

Wendy Raskind ◽

Eileen Bryant ◽

Mary E.D. Flowers ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Peripheral Blood ◽

Marrow Transplantation ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Significant Proportion ◽

White Blood Count ◽

Median Percentage ◽

Cytogenetic Remission

Abstract Fourteen patients with cytogenetic relapse of chronic myeloid leukemia (CML) after transplantation with unmanipulated bone marrow were treated with α-2a–interferon. There were eight men and six women, median age, 33 years. Twelve patients received marrow from a related allogeneic donor and two received marrow from a syngeneic donor. The median percentage of Ph-positive metaphases at the time of starting interferon was 55% (10% to 87%). Daily interferon was started at a dose of 1 to 3 × 106 U/M2/d, depending on initial blood counts and was adjusted as tolerated to maintain the white blood count in the range of 2,000 to 3,000/μL and the platelet count greater than 60,000/μL. After a stable cytogenetic remission was achieved, the interferon dose was decreased to a maintenance level. Twelve patients achieved a complete cytogenetic remission on at least one occasion. Median time to achieve a complete cytogenetic remission was 7.5 months (range, 1.5 to 12). Eight patients remain in cytogenetic remission for 10+ to 54+ months from the time of first documented remission. After complete cytogenetic remission was established, nine patients were tested for the presence of the mRNA transcript of the bcr/abl fusion gene by polymerase chain reaction (PCR) testing. Four patients were PCR-negative on at least one occasion: two patients were PCR-negative on a single occasion; one patient had serial tests, which were PCR-negative; and one patient had serial PCR-negative peripheral blood tests with a single PCR-positive bone marrow obtained concurrently with a negative peripheral blood test. Median follow-up time for all patients is 44 months (range, 20 to 64). Interferon was generally well tolerated; only one responding patient was unable to continue interferon because of toxicity. Interferon induces durable cytogenetic remissions in a significant proportion (57%) of patients with cytogenetic relapse following bone marrow transplantation (BMT) without causing life-threatening toxicities.

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Relapse with BCR-ABL1 Elevation in Chronic Myeloid Leukemia after Progression to Multiple Myeloma from Monoclonal Gammopathy of Undetermined Significance with a Persistent KMT2D Mutation

Blood ◽

10.1182/blood-2021-145904 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4608-4608

Author(s):

Xiaofei Xu ◽

Lan Zhang ◽

Shengjie Wang ◽

Keyi Jin ◽

Chen DAN ◽

...

Keyword(s):

Multiple Myeloma ◽

Monoclonal Gammopathy ◽

Myeloid Leukemia ◽

Plasma Cells ◽

M Protein ◽

Abnormal Growth ◽

School Of Medicine ◽

Medical Discipline ◽

Immunofixation Electrophoresis ◽

Undetermined Significance

Abstract Chronic myeloid leukemia (CML) and monoclonal gammopathy of undetermined significance (MGUS) are two different hematologic malignancies, the former arising from the myeloid cell lineage, and the latter arising from plasma cells. The concurrent diagnosis of CML and MGUS progression to multiple myeloma (MM) in one patient is an extremely rare event. A 59-year-old male was diagnosed with CML and MGUS with no discomfort in August 2012. Bone marrow (BM) aspiration suggested chronic myelogenous leukemia in chronic phase and perhaps myeloproliferative with 6.5% mature plasma cells (Figure 1A). FISH analysis detected that the BCR-ABL1 expression was 130%. And Next-generation sequencing (NGS) of BM showed: ASXL1 , KMT2D , SPEN , BRINP3 , ANKRD26 , PLCG1 , CUX1 were mutated (Figure 2I). The patient started oral imatinib 400 mg per day and achieved a complete cytogenetic response at 3 months. In September 2019, his IgG levels were 2,790 mg/dl (Figure 2J and serum immunofixation electrophoresis revealed monoclonal (M) protein of IgG-Lambda type (Figure 1E). BM aspiration revealed 9.5% plasma cell infiltration, including 6% mature plasma cells and 3.5% proplasmacyte (Figure 1C and 2H). Flow cytometry in BM showed 6.3% plasmacytoma and abnormal cell expressing CD38+CD138+CD56+CD117+clambda+ (Figure 1F). BM biopsy showed hematopoietic hyperplasia with abnormal growth of immature cells (Figure 1B). Fluorescent in situ hybridization (FISH) was negative. Mutations of KMT2D, SPEN, BRINP3, ANKRD26, PLCG1, CUX1, and ZMYM3 still existed(Figure 2I). In January 2020, examination of a new BM aspiration revealed that mature plasma cells were 3% and plasmablast and proplasmacyte were 4.5% (Figure 2H). In February 2020, he stopped IM therapy with undetectable BCR-ABL1 copies because he met the requirement of stopping TKI therapy . In March 2020, IgG levels were 3520 mg/dl and serum immunofixation electrophoresis still revealed monoclonal (M) protein of IgG-Lambda type. His BM aspiration demonstrated 13.5% plasma cells in April 2020 (Figure 2B and 2H). Flow cytometry in BM showed 6.44% (Figure 2F). BM biopsy showed extremely increased proliferation with abnormal growth of abnormal cells (Figure 2A). FISH demonstrated the presence of t(4;14)(p16;q32)(IGH/FGFR3) , 13q14 deletion（RB-1） and 13q14.3 （D13S319） (Figure 2C, 2D and 2E). The patient was diagnosed as MM (IgGλ type, D-S stage IA; ISS stage II) . BCR-ABL1 copies were still not detected at this point (Figure 2G). The patient continued his follow-up treatment of MM without chemotherapy.However, in June 2020, he was considered to have a molecular relapse with 0.2013% BCR-ABL1 copies in the peripheral blood (Figure 2G). NGS showed that the variant allele fractions of KMT2D, SPEN, BRINP3, ANKRD26, PLCG1, CUX1, and ZMYM3 mutations were similar to former . He restarted 400 mg daily IM therapy and BCR-ABL1 copies were undetectable againafter one month therapy (Figure 2G). BM aspiration revealed that the percentage of plasma cells increased to 25.5% in August 2020 (Figure 2H). Then the patient was started on treatment for ISS stage II standard risk myeloma with ID regimen: ixazomib 4 mg on days 1, 8 , 15 and dexamethasone 20 mg on days 1, 8, 15 , 22 in 28-day cycles. After 6 cycles , the patient got VGPR. BM aspiration demonstrated 13% plasma cells (Figure 2H). And he continued to receive myeloma treatment and imatinib . BCR-ABL1 were <MR4.5 (Figure 2G). Our research indicated that KMT2D mutation may make MGUS progress to MM with NK cells functional defects and then promote the recurrence of BCR-ABL1. Co-existence of these two diseases is rare, therefore, additional investigations are warranted. Acknowledgment:The research was supported by the Public Technology Application Research Program of Zhejiang, China (LGF21H080003), the Key Project of Jinhua Science and Technology Plan, China (2020XG-29 and 2020-3-011), the Academician Workstation of the Fourth Affiliated Hospital of the Zhejiang University School of Medicine (2019-2024), the Key Medical Discipline of Yiwu, China (Hematology, 2018-2020) and the Key Medical Discipline of Jinhua, China (Hematology, 2019-2021). Correspondence to: Dr Jian Huang, Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine. N1 Shangcheng Road. Yiwu, Zhejiang, Peoples R China. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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c-Myc Amplification in Non Hodgkin’s-Lymphomas with Burkitt-Like Features Is Associated with a Poor Prognosis.

Blood ◽

10.1182/blood.v104.11.3266.3266 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3266-3266

Author(s):

Hossein Mossafa ◽

Diane Damotte ◽

Anne Vincenneau ◽

Isabelle Amouroux ◽

Nareth Athken ◽

...

Keyword(s):

Bone Marrow ◽

Lymph Nodes ◽

Peripheral Blood ◽

Poor Prognosis ◽

Chromosomal Abnormalities ◽

Fusion Gene ◽

Receptor Gene ◽

Lymphoid Cells ◽

Morphological Examination ◽

Hodgkin's Lymphomas

Abstract We retrospectively studied 15 newly diagnosed patients presenting with NHL and Burkitt-like cells (BLCs) after morphological examination and histology review (lymph-nodes: 7 cases, peripheral blood: 5 cases, bone marrow: 3 cases and spleen: 1 patient). Conventional cytogenetic analyses were performed at diagnosis on lymph nodes biopsies (n=6), peripheral blood lymphocytes (n=4), bone marrow (n=4) or spleen (n=1). FISH studies used commercially available probes: IGH/c-MYC fusion signals probes, IGH/Bcl-1 fusion signals probes, IGH/Bcl-2 fusion signals probes and c-Myc 8q24 probe to detect t(8;14)(q24;q32), t(11;14)(q13;q32), t(14;18)((q32;q21) and c-Myc amplification, respectively. Morphological examination and/or histology showed BLCs in all patients. Burkitt-like lymphoma (BLL) is a highly proliferative lymphoma that morphologically resembles Burkitt’s lymphoma (BL) but has more polymorph and pleiomorph cells or large lymphoid cells than BL. The mean percentage of Ki-67 positive cells was 80% (range, 70–100%). A normal karyotype was present in 3 cases and a complex karyotype was observed in 12 cases (80%). When combining conventional cytogenetic studies and FISH studies, t(8;14) or the variants t(2;8) or t(8;22) were never detected. In contrast t(11;14)(q13;q32) was found in 4 cases and t(14;18) in 6 cases. Interestingly, c-Myc amplification was observed in all cases with 3 to more than 9 copies in 10–77% metaphase or interphase cells. The diagnosis of follicular lymphoma (FL) was confirmed by a CD5− and CD10− immunologic profile, typical t(14;18) in 4/6 cases and IgH/Bcl-2 fusion gene in all cases. Four cases were classified as mantle cell lymphoma (MCL) with a blastoid variant: MCL diagnosis was established by lymph-node biopsy in 1 case, CD5+ and CD23+ expression in 3/4 cases and 2/4 cases respectively, typical t(11;14)(q13;q32) in 3 cases, complex caryotype including 11 and 14 chromosomal abnormalities in 1 case and IgH/Bcl-1 fusion gene in all cases. Two patients had marginal MZL with a CD5− and CD10− profile and a complex caryotype including +3 and +18. Two patients presented a DLBCL (CD19+, CD20+) with BLCs and one case was classified as T-NHL (CD2+, CD4+, T-cell receptor gene rearrangements) in leukemic phase with BLCs. All these 15 patients have a poor prognosis with a death occurring in 6 patients during the first month after diagnosis. The presence of BLCs was observed independently of the type of lymphomas, FL, MCL or MZL. c-MYC amplification was associated with BLCs and progressive disease. In conclusion, we identified a new subgroup of patients with NHL (14 B-NHL, 1 T-NHL) and a profile including a poor prognosis, Burkitt-like features at presentation without t(8;14)(q24;q32) or its variants and Myc amplification in all cases.

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A NUP98-HOXD13 Fusion Gene Induces a Transplantable Myelodysplastic Syndrome in Mice.

Blood ◽

10.1182/blood.v110.11.401.401 ◽

2007 ◽

Vol 110 (11) ◽

pp. 401-401

Author(s):

Yang Jo Chung ◽

Chul Won Choi ◽

Christopher Slape ◽

Terry Fry ◽

Peter D. Aplan

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Peripheral Blood ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Hematopoietic Stem ◽

Significant Difference ◽

Acute Myeloid

Abstract The myelodysplastic syndromes (MDSs) are a group of hematologic stem cell disorders characterized by ineffective hematopoiesis and dysplasia. A large number of chromosomal aberrations including deletions, amplifications, inversions, and translocations, some of which involve the NUP98 gene, have been associated with MDS. Recently an MDS mouse model expressing a NUP98-HOXD13 (NHD13) fusion gene was developed, which faithfully recapitulates all of the key features of MDS. Although it is well-established that acute myeloid leukemia (AML) is transplantable, there is no evidence that MDS is a transplantable condition. Therefore, in order to develop evidence for MDS as a hematopoietic stem cell (HSC) disease, we attempted to transfer MDS to normal recipients through bone marrow transplantation (BMT). All the recipients transplanted with bone marrow (BM) cells from NHD13 mice with MDS showed anemia, leukopenia, lymphopenia, and neutropenia when compared to recipients of wild-type (WT) littermates. The homing efficiency of the NHD13 primitive progenitor cells (Lineage negative [Lin−], Sca-1+) was about 2 fold higher than WT, and there was no significant difference in BM cellularity between the recipients of NHD13 and WT BM, indicating that the NHD13 recipients had ineffective hematopoiesis. These phenomena were reproduced in secondary recipients using primary recipients of NHD13 BM as donor mice. In secondary transplantation assays, 3 out of 5 recipients developed acute myeloid leukemia (AML) at 16 weeks post-transplantation. Morphological features of MDS, including nuclear-cytoplasmic asynchrony, binucleate cells, hypersegmented neutrophils, and giant platelets were detected in BM and peripheral blood of NHD13 donor, primary and secondary recipients by cytospin preparations. In competitive repopulation assays, mice transplanted with equal numbers of WT and NHD13 BM cells showed a decreased percentage of NHD13 cells in the peripheral blood, but an increased percentage of NHD13 cells in the BM, again providing evidence of ineffective hematopoiesis of the NHD13 cells. The transplantation of lineage depleted cells from BM has shown that the transplantable cells for MDS reside in the Lin− population of NHD13 BM. These findings demonstrate that MDS can be transferred to healthy recipients by BMT, supporting the concept that MDS originates in a transplantable multilineage hematopoietic stem cell.

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Use of α-2a-Interferon to Treat Cytogenetic Relapse of Chronic Myeloid Leukemia After Marrow Transplantation

Blood ◽

10.1182/blood.v90.7.2549.2549_2549_2554 ◽

1997 ◽

Vol 90 (7) ◽

pp. 2549-2554 ◽

Cited By ~ 3

Author(s):

Celestia S. Higano ◽

Deborah Chielens ◽

Wendy Raskind ◽

Eileen Bryant ◽

Mary E.D. Flowers ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Peripheral Blood ◽

Marrow Transplantation ◽

Myeloid Leukemia ◽

Fusion Gene ◽

Significant Proportion ◽

White Blood Count ◽

Median Percentage ◽

Cytogenetic Remission

Fourteen patients with cytogenetic relapse of chronic myeloid leukemia (CML) after transplantation with unmanipulated bone marrow were treated with α-2a–interferon. There were eight men and six women, median age, 33 years. Twelve patients received marrow from a related allogeneic donor and two received marrow from a syngeneic donor. The median percentage of Ph-positive metaphases at the time of starting interferon was 55% (10% to 87%). Daily interferon was started at a dose of 1 to 3 × 106 U/M2/d, depending on initial blood counts and was adjusted as tolerated to maintain the white blood count in the range of 2,000 to 3,000/μL and the platelet count greater than 60,000/μL. After a stable cytogenetic remission was achieved, the interferon dose was decreased to a maintenance level. Twelve patients achieved a complete cytogenetic remission on at least one occasion. Median time to achieve a complete cytogenetic remission was 7.5 months (range, 1.5 to 12). Eight patients remain in cytogenetic remission for 10+ to 54+ months from the time of first documented remission. After complete cytogenetic remission was established, nine patients were tested for the presence of the mRNA transcript of the bcr/abl fusion gene by polymerase chain reaction (PCR) testing. Four patients were PCR-negative on at least one occasion: two patients were PCR-negative on a single occasion; one patient had serial tests, which were PCR-negative; and one patient had serial PCR-negative peripheral blood tests with a single PCR-positive bone marrow obtained concurrently with a negative peripheral blood test. Median follow-up time for all patients is 44 months (range, 20 to 64). Interferon was generally well tolerated; only one responding patient was unable to continue interferon because of toxicity. Interferon induces durable cytogenetic remissions in a significant proportion (57%) of patients with cytogenetic relapse following bone marrow transplantation (BMT) without causing life-threatening toxicities.

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An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

Case Reports in Hematology ◽

10.1155/2018/7863943 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Kosuke Miki ◽

Naoshi Obara ◽

Kenichi Makishima ◽

Tatsuhiro Sakamoto ◽

Manabu Kusakabe ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Plasma Cells ◽

Bone Marrow Examination ◽

Bone Lesions ◽

Dexamethasone Treatment ◽

Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

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Multiple myeloma: circulating lymphocytes that express plasma cell antigens

Blood ◽

10.1182/blood.v64.2.352.bloodjournal642352 ◽

1984 ◽

Vol 64 (2) ◽

pp. 352-356

Author(s):

GJ Ruiz-Arguelles ◽

JA Katzmann ◽

PR Greipp ◽

NJ Gonchoroff ◽

JP Garton ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Plasma Cell ◽

Peripheral Blood ◽

Plasma Cells ◽

Peripheral Blood Lymphocytes ◽

Tumor Burden ◽

B Cell Differentiation ◽

Blood Lymphocytes ◽

Bone Marrow Plasma

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1–3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.

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Analysis of interferon-inducible genes in cells of chronic myeloid leukemia patients responsive or resistant to an interferon-alpha treatment

Blood ◽

10.1182/blood.v76.11.2337.bloodjournal76112337 ◽

1990 ◽

Vol 76 (11) ◽

pp. 2337-2342

Author(s):

IM Clauss ◽

B Vandenplas ◽

MG Wathelet ◽

C Dorval ◽

A Delforge ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Interferon Alpha ◽

Peripheral Blood ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Healthy Controls ◽

Ifn Alpha ◽

Inducible Genes ◽

Marrow Cells

Recombinant human interferon-alpha (IFN-alpha) can induce a hematologic remission in patients with chronic myeloid leukemia. However, some patients are resistant and others develop late resistance to the IFN- alpha treatment. To understand the molecular mechanism of this resistance, we have analyzed the expression of 10 IFN-inducible genes in the cells of three resistant patients, two responsive patients, and six healthy controls. Northern blot hybridizations showed that all the genes were induced in in vitro IFN-alpha treated peripheral blood cells of the patients and healthy controls. These genes were also inducible in peripheral blood and bone marrow cells of two out of two resistant patients administered an injection of IFN-alpha. We conclude that the resistance to the IFN-alpha treatment of the chronic myeloid leukemia patients we studied is not due to (1) the absence of induction of any of the 10 IFN-inducible genes we studied, including the low-molecular- weight 2′-5′oligoadenylate synthetase; (2) the presence of an antagonist of IFN-alpha in the peripheral blood or bone marrow cells; and (3) the presence of neutralizing anti-IFN-alpha antibodies.

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Real-Life Management of Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience

Acta Haematologica ◽

10.1159/000491546 ◽

2018 ◽

Vol 140 (2) ◽

pp. 105-111 ◽

Cited By ~ 1

Author(s):

Fiorina Giona ◽

Michelina Santopietro ◽

Giuseppe Menna ◽

Maria Caterina Putti ◽

Concetta Micalizzi ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Peripheral Blood ◽

Myeloid Leukemia ◽

Real Life ◽

Chronic Phase ◽

Optimal Management ◽

Molecular Monitoring ◽

Italian Experience ◽

Adults And Children

Background: To date, no data on the adherence to specific guidelines for children with chronic myeloid leukemia (CML) in chronic phase (CP) have been reported. Methods: Since 2001, guidelines for treatment with imatinib mesylate (IM) and monitoring in patients younger than 18 years with CP-CML have been shared with 9 pediatric referral centers (P centers) and 4 reference centers for adults and children/adolescents (AP centers) in Italy. In this study, the adherence to these guidelines was analyzed. Results: Thirty-four patients with a median age of 11.4 years and 23 patients with a median age of 11.0 years were managed at 9 P and at 4 AP centers, respectively. Evaluations of bone marrow (BM) and/or peripheral blood (PB) were available for more than 90% of evaluable patients. Cytogenetics and molecular monitoring of PB were more consistently performed in AP centers, whereas molecular analysis of BM was carried out more frequently in P centers. Before 2009, some patients who responded to IM underwent a transplantation, contrary to the guidelines’ recommendations. Conclusions: Our experience shows that having specific guidelines is an important tool for an optimal management of childhood CP-CML, together with exchange of knowledge and proactive discussions within the network.

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